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OUTLINE 5. Nucleolus
o high concentration of genetic material and ribosomes
(protein synthesis); no limiting membrane
1.01 Cell Physiology & Transport o highly staining area
1.02 Receptor Physiology & Signaling o enlarged during protein synthesis
1.03 Nerve Physiology
1.04 Synaptic Physiology 6. Endoplasmic Reticulum
1.05 Autonomic Nervous System o glycogen breakdown; helps detoxify substances
1.06 Muscle Physiology I o Rough ER: granular; complex of RNA + proteins ®
1.07 Muscle Physiology II synthesizes proteins
1.08 Plenary: Nerve & Muscle Physiology o Smooth ER: agranular; synthesizes lipids and cholesterol,
involved in breakdown of glycogen & helps in
detoxifications
1.01 Cell Physiology & Transport
7. Golgi Apparatus
HOMEOSTASIS o modified proteins with carbohydrate groups
o packages/concentrates products into vesicles
• maintenance of intracellular components (ions, small o wrongly folded protein goes to lysosome instead
molecules, water, pH, etc.) and bodily parameters (temp,
blood pressure, blood volume, etc.) 8. Mitochondria
• maintained even with addition and elimination of food and o Power house of the cell
water (through eating, and urine & feces respectively) o Mitochondrial matrix: place for TCA cycle and ß-oxidation
• maintenance is achieved through transport of substances and of fatty acids
water, in and out of cells o Maternal mitochondrial inheritance
o Can self-replicate with its own DNA
• changes are allowed as long as it is within normal range
o if change exceeds normal range, body performs
9. Lysosomes
mechanisms that restore normal conditions
o membrane-bound material that contains digestive
CHARACTERISTICS OF EVERY CELL enzymes (e.g. hydrolase)
o Autophagy: self-degradation intracellular organelles
o targeted destructions
Every cell must have all of the following:
1. Utilization of O2 to produce energy essential for cell
10. Proteasomes
function where energy generation mechanisms are
o degradative function like lysosome but not membrane-
similar in all types of cells
bound
2. Cellular products are present inside and outside of the
o degrades targeted intracellular proteins
cell
3. Capable of reproducing through mitotic division (mitosis)
11. Peroxisomes
with the exception of stem cells
o membrane-bound and can self-replicate
CELL STRUCTURE o for detoxification and fatty acid oxidation, contains
oxidative enzymes (Oxidases and Catalase)
1. Protoplasm
12. Cytoskeleton
o Nucleoplasm + cytoplasm
o provide rigid physical structure to cells but is not rigid;
o Nucleoplasm: inside the nuclear membrane
capable of movement and reorganization
o Cytoplasm: outside the nuclear membrane, within cell
o Actin Filaments (Microfilament): locomotion, core of
membrane
microvilli, connects cell to other cells
o Water, Ions, Macromolecules (Carbohydrates, Lipids,
o Myosin (Thick filament): molecular motor
and Proteins)
o Intermediate Filaments: structural functions; connect to
other cells and extracellular matrix
2. Cell Membrane
o made up of lipid bilayer o Microtubules: grow from center to periphery; intracellular
transport; present in cilia and flagella
o regulate internal environment of cell via transport
mechanisms for homeostasis
INTERCELLULAR CONNECTIONS
o energy is stored through triacylglycerides (TAGs)
a) Tight Junctions
3. Nucleus
o eliminate intercellular spaces to increase the
o contains genome of cell (DNA), RNA, and proteins
impermeability
o responsible for DNA repair, replication, & transcription
b) Anchoring Junctions
o control and promote cell reproductions
o link cell by microfilaments
o Desmosomes, Hemidesmosomes, Adhering Junctions
4. Nuclear Membrane / Envelope
c) Gap Junctions
o Outer layer: contains ribosomes, continuous with ER
o Inner layer: smooth surface; in close proximity with a • permits substances to pass between cells without
fibrillar protein skeleton (nuclear lamina) entering ECF (connexons)
o nuclear pores allow passage of select molecules
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PLASMA MEMBRANE
• The same as cell membrane and its description in the Fick’s Law of Diffusion
previous page • surface area ® concentration gradient ® shorter
• Functions: distance ® slower diffusion rate
o Semi-permeability for selective transport of molecules • larger molecules ® slower diffusion rate
o Cell-to-cell recognition and communication
o Tissue organization to define the cell’s shape in addition
to the cytoskeleton
• Fluid Mosaic Model
o constant in motion; dynamic and not rigid
o made up of different elements
• Components:
1) Lipid rafts
o for plasma membrane’s rigidity and bulk transport Stokes-Einstein Equation
2) Phospholipid bilayer • used to approximate diffusion coefficient of spherical
o Contains integral proteins, carbohydrates, and some molecules
cholesterol !"
o impenetrable for water-soluble / polar substances D=-
#$%&
(e.g. ions, glucose)
o permeable for fat-soluble / non-polar substances o D = diffusion coefficient
(e.g. O2, CO2, alcohols, cholesterol) o κ = Boltzmann's constant
3) Integral Proteins o T = Temperature (K)
o channels and carriers of polar molecules o η = medium viscosity
4) Peripheral Proteins o r = radius of molecule
o aids in transport through channels, attached to
integral proteins on one side only
5) Glycocalyx ELECTROCHEMICAL GRADIENT
o CHO found outside membrane; makes cell negative
charged, adherent and able to recognize other cells
• quantify driving force acting on molecule to move across the
6) Glycoproteins
membrane (DF is determined by chemical concentration and
o carbohydrates attached to protein
electrical charge)
7) Proteoglycans
• Electromotive Force: electrical difference to balance
o carbon and protein compounds loosely attached to
outer surface of the cell • Nernst Equation: quantitates energy in concentration gradient,
millivolts
DIFFUSION
OSMOSIS
CTROCHEMICAL GRADIENT
• Definition: process by which molecules spontaneously move
from an area of high to low concentration until equilibrium is • diffusion of water, follows laws of thermodynamics
reached; follows a downhill gradient • Osmotic Pressure: pressure required to prevent inward flow of
water across semi-permeable membrane (dependent on
• Diffusion is pressure-dependent
o Higher pressure = increased diffusion particles in solution)
• Oncotic Pressure: osmotic pressure generated by large
1. Simple Diffusion molecules in solution (↑ number of LM = increased OP)
o movement of molecules or ions through a membrane
opening without any carrier proteins TONICITY
o substance concentration ® rate of diffusion (linear)
o can pass through channels that may be voltage-gated, • effect of a solution on cell volume
ligand-gated, stretch/pressure-gates, phosphorylation- • An effective osmole does not cross the semipermeable
gated membrane
2. Facilitated Diffusion • Isotonic: equal osmolarity as cell (does not change)
o requires carrier proteins to diffuse in presence of the • Hypertonic: higher molarity than cell (shrinks)
concentration gradient • Hypotonic: lower osmolarity than cell (swells)
o has maximum velocity (Vmax), faster than simple diffusion • Isotonic = Iso-osmotic only if osmoles are effective
but reaches saturation point (plateau in a graph) • 0.9% Sodium Chloride Solution
o NSS/Normal Saline Solution
Figure below: graphical representation of Simple Diffusion and o approximates the osmolarity of blood
Facilitated Diffusion o NaCl is an effective osmole, therefore it is isotonic and
iso-osmotic to blood
ACTIVE TRANSPORT
1. Local Communication
o Contact-dependent signals
o Membrane-associated ligands where surface molecules
bind to the other cell’s surface molecules in the
membrane
o Communication junctions have direct interactions:
§ Gap junctions
§ Adhering junctions
§ Tight junctions
o Chemical signals occur by diffusion of molecules through
the ECF to act on nearby cells
§ Autocrine
§ Paracrine
SIGNAL MOLECULES/LIGANDS
Examples of transporters and list of extra/intra-cellular 1. Lipophilic - Can diffuse through the phospholipid bilayer; binds
concentrations to receptors in nucleus or cytosol; relatively slow response.
2. Lipophobic - Cannot diffuse through phospholipid bilayer so
CYTOSIS / VESICULAR TRANSPORT they bind to receptor proteins in cell membrane; rapid response.
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CHARACTERISTICS OF NEURONS
o Active form: GTP attached α subunit
§ Regulated by guanine nucleotide exchange a) Dendrites: receptive region; conducts signals towards the cell
factors (GEFs) by releasing GDP and binding of body; increase surface area for reception
GTP. Therefore, making GEFs activators b) Dendritic spines: out-branching of dendrite’s primary
§ α-GTP dissociates from βγ subunits and have two branches
possible pathways: (1) Directly activate ion channels, c) Cell body/Soma/Perikaryon: biosynthetic center; contains
or (2) Excite or inhibit certain enzymes (effector the usual organelles plus Nissl bodies and Neurofibrils
proteins) d) Axon: impulse generation and conducting region; transmits
signals away from cell body; where action potential is
3. Catalytic Receptors conducted
a) Receptor Guanylyl Cyclase: catalyze the generation of e) Axon hillock: found at the initial segment of the axon; where
cGMP from GTP signals are added up together.
b) Receptor Serine/Threonine Kinases: phosphorylate o Since it has more Na+ channels (300-500), this is where
serine or threonine residues on cellular proteins the action potential is generated then conducted along
c) Receptor Tyrosine Kinases (RTKs): phosphorylate the axon until it reaches the axon terminal. (1st segment
tyrosine residues on themselves and other proteins via of axon hillock is unmyelinated.)
autophosphorylation f) Axon terminals: secretory regions that look like a “button”
d) Tyrosine Kinase Associated Receptors (TKARs): ending of the branches, where neurotransmitters are released.
interacts with cytosolic tyrosine kinases. Receptor itself is g) Terminal branches: where axon terminals are attached; as
not catalytic. many as 10000
e) JAK-STAT: JAK – catalytic receptor; STAT: signaling h) Myelin sheath: insulates and protects the cell; allows
transduction activator for transcription saltatory conduction for faster transmission of impulses
f) Receptor Tyrosine Phosphatases: cleave phosphate i) Nissl bodies/Chromatophilic bodies: RER and loose
groups from tyrosine groups of cellular proteins ribosomes that replenish plasma membrane proteins
j) Nodes of Ranvier/Neurofibrillar nodes: gaps in
4. Regulated Intramembrane Proteolysis (RIP) unmyelinated axon fiber that also helps in transmission of
o Able to recognize extracellular signals and convert it to impulses in saltatory conduction
an intracellular effect
o Membrane protein that doesn’t directly coincide with the CELLS OF NERVOUS SYSTEM: GLIAL CELLS
definition of a receptor
1. Astrocytes
5. Intracellular/ Nuclear Receptors o star-shaped; largest and most common glial cells found
o Bind to specific DNA sequences (hormone response in the gray matter
elements) in regulatory region of responsive genes o help in repair and scarring process of the brain and
o Modulate gene expression by acting as transcriptional spinal cord
repressors o Mediates metabolic exchange between neurons and
o 2 types: capillaries and control of chemical environment by
§ Located in the cytoplasm in the absence of ligand clearing intercellular space
and when bound to ligand, translocate to the o Has two types:
nucleus a. Protoplasmic: found in gray matter with many
§ permanently resides in the nucleus. branching processes
b. Fibrous: found in white matter with long, thin,
LOSS OF MITOGENIC SIGNALING unbranched processes in nodes of Ranvier
2. Ependymal cells
• Apoptosis – programmed cell death o ciliated cuboidal or columnar epithelial cells that facilitate
• Caspases – death enzymes movement of the cerebrospinal fluid through the central
• “altruistic” death canal
o with microvilli for absorption
TERMINATION OF CELL SIGNALING 3. Microglia
o smallest irregularly shaped neuroglial cells found both in
• The termination of a signal at the appropriate time can be just white and gray matter
as important as the initiation of a signal. o Act as the main phagocytes of CNS
• Degradation or removal of the ligand so that it can no longer 4. Oligodendrocytes
access its receptor o secrete myelin found in CNS; can surround and
• Enzymes reverse the cellular modifications that result from myelinate several axons
signaling cascades 5. Schwann cells/Neurolemmocyte:
o secrete myelin found in PNS and can only wrap around a
single axon
1.03 Nerve Physiology
SENSORY NERVE FIBER CLASSIFICATION
THE NERVOUS SYSTEM
Table below: Numerical classification of sensory nerve fibers
• Enables the body to react to changes in its internal and Number Origin Fiber Type
external environments. Ia Muscle spindle, annulo-spiral ending Aa
• Controls and integrates various activities of the body Ib Golgi tendon organ Aa
II Muscle spindle, flower-spray ending; Ab
Organization of the Nervous System touch, pressure
• Central Nervous System (CNS): brain and spinal cord III Pain and cold receptors; some touch Ad
• Peripheral Nervous System (PNS): interface between the receptors
environment and CNS IV Pain, temperature, and other receptors C
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Table below: Functional Classification of sensory neurons. Factors Affecting Membrane Potential
(Etlager & Gasser) (Lloyd & Hunt)
Type Function Type Function 1. Electrochemical Potential
Aa Proprioception IA/IB
Proprioception • Concentration Gradient
o allows measuring the effect of the gradient to the
Ab Proprioception IIProprioception
movement of the ions
Skin Skin
o favors diffusion of Na+ inside and K+ outside
mechanoreceptor mechanoreceptor
o affects size potential
Ad Skin III Skin o main concern of Nernst Equation
mechanoreceptor mechanoreceptor • Electric Gradient
Pain o charge of the membrane [-] inside and [+] outside
Temperature o K+ is hindered from moving out because of the
C Skin IV Skin intracellular space being more [-]
mechanoreceptor mechanoreceptor o Formed because of a difference in charge; because
Pain the charge is negative intracellularly, both the
Temperature concentration gradient and electrical gradient favor
From Aa ® C, ¯ diameter; Higher diameter = higher velocity. the entry of Na+.
A. Membrane Permeability
• Selective flux of K+ out of the cell following its diffusion • Used to calculate membrane potentials involving
gradient several ion concentrations
• Passes through leak/non-gated channel (pore) • Based on membrane permeability to an ion
• When more positive charges leaks out, intracellular • (e.g. if the membrane is impermeable to both Na+ and Cl-,
becomes negatively charged with the extracellular space then the membrane potential will be equal to the K+
becoming positively charged. Nernst Potential)
• diffusion potential depends on 3 factors:
RESTING MEMBRANE POTENTIAL 1) polarity of electrical charge of each ion
2) permeability (P) of membrane to each ion
• The resting membrane potential is generated by the 3) concentrations (C) of inside and outside
electrical gradient formed by selective permeability of the
membrane and maintained by the influx/efflux of ions to keep 5. Chord Conductance Equation
the gradient • Membrane Conductance (how leaky to ions)
• -70 mV = resting potential of all cells and axons o no. of ion channels in the membrane
• -90 mV = resting potential of all cardiac and skeletal muscle o length of the time these channels are in open state
• Slight excess of negative charge lined along the inside of the • Capacitance – ability of the membrane to store an
membrane and slight less of positive charge on the outside electrical energy ; inverse of resistance
• Proteins which too large to go out, contribute to the
electronegativity of the intracellular medium 6. The Sodium-Potassium Pump
• Primary active transport process that pumps Na+ ions
out and K+ ions in (3 Na+ out, 2 K+ in)
• Electrogenic pump – creates electrical potential across
the membrane
• Uses ATP; goes against the electrochemical
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• Net difference of 1 [+]-charged ion, making the ACTION POTENTIAL
membrane [-]-charged (-3 ions in replaced by +2 ions)
• Rapid change of membrane potential spreading along nerve
7. Voltage-Gated Ion Channels fiber membrane
• Sensitive to voltage difference across the membrane • Reversal of polarity (+ inside, - inside)
• Na+ and K+ gates • Initiated when the threshold potential is reached
• Na+ has 2 gates: activation and inactivation • Starts at opening of the voltage-gated Na+ channels ® Na+
influx makes depolarization possible
LOCAL POTENTIAL • K+ gates open after depolarization for membrane
repolarization
• Transient shift of membrane potential in a localized area • Presence of All or none response
• “Subthreshold response” by opening of Na+ channels o Further increase in intensity above threshold potential ®
• Opening of the voltage sensitive Na+ channels no increase or any change in action potential
• Change in membrane properties not enough to generate o Action potential occurs with constant amplitude and
action potential form regardless of the intensity of stimulus
• Magnitude of change in the membrane potential is
dependent on the strength of stimulus Stages of Production of Action Potential
1. Membrane depolarization
o influx of Na+ by voltage gated ion channel
o membrane becomes less negative
2. Subthreshold Potential
o Na+ channels close | K+ channels open
3. Repolarization
o more K+ channels open
o Membrane becomes more negative (due to prolonged
K+ efflux)
4. Na+ and K+ levels reach equilibrium
5. Resting potential
o closing of Na+ and K+ channels
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5. Repolarization Stage Figure below: Propagation of AP and “current sink”. Local current
o Na+ channels become inactivated, while voltage-gated K+ flow (movement of positive charges) around an impulse in an
channels open axon
o K+ efflux gradually restores negative membrane potential
o Repolarization will trigger further opening of K+ channels
resulting to further repolarization
6. Hyperpolarization/Undershoot Stage
o More negative point than normal Resting Membrane
Potential due to the slow closing of K+ channels
o After hyperpolarization, the polarity of membrane returns
to resting potential due to the Na+/K+ electrogenic pump.
• A second response can be elicited provided that a second Factors affecting the propagation of action potential
stimulus is stronger than the threshold (intensity of stimulus,
o Larger diameter ® excitability ® Shorter duration (faster
not threshold potential).
conduction)
• Na+ channel is closed, K+ channel is opened
o Myelinated – faster nerve impulse
• “Multiple Fiber Action Potential” (Compound Action o Unmyelinated – slower nerve impulse
Potential) Table below: Local potential vs Action potential
• Has variable threshold Local Potential Action Potential
graded response – can be all or none response – cannot
“You will be able to produce another action potential if and summated be summated
only if you apply a stimulus that is much greater than the No threshold potential has threshold potential
threshold. “ – Dr. Bartolome
no refractory period has refractory period
Figure below: Absolute & Refractory Periods (Bern & Levy, 7th Ed) amplitude decreases with amplitude is constant
distance
conducted with decrement conducted without decrement
duration varies on initiating constant duration for a given
conditions cell type
initiated by extrinsic stimuli or initiated by membrane
neurotransmitter depolarization
non-voltage gated channels voltage-gated channels
• Synapse
o Specialized junctions between 2 neurons or a neuron
and effector organ
• Synaptic cleft
o gap between two neurons where information exchange
occurs
PROPAGATION OF ACTION POTENTIAL • Presynaptic Neuron
o Terminal portion of an axon
• Positive charges from the membrane ahead and behind the o Belongs to the initiating neuron
action potential flow into the area of negativity (“current o Contains neurotransmitters in vesicles, mitochondria, and
sink”) rough endoplasmic reticulum
• Location and number of Na+ voltage-gated channels: • Postsynaptic Neuron
o 350-500 in the initial segment o Where an electrical impulse is transmitted across a
o 20-75 in axon terminal synaptic cleft by the release of a chemical
o < 25 in the myelin sheath neurotransmitter from the axon terminal of a presynaptic
o 2000-12000 in the nodes of Ranvier neuron
o few Na+ voltage-gated channels
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Figure below: axon terminal of the presynaptic neuron
2. The terminal portion of the presynaptic neuron gets
depolarized due to the action potential (AP)
1. Axoaxonic synapse: axon ® axon 7. Binding of transmitter to receptors causes the opening of ion
2. Axosomatic synapse: axon ® soma channels in the postsynaptic membrane that alter the
3. Axodendritic synapse: axon ® dendrite excitability of the cell.
4. Dendodentritic synapse: dendrite ® dendrite
5. Dendrosomatic synapse: dendrite ® dendrite POST-SYNAPTIC RECEPTORS
Removal of Neurotransmitter
• once they bind to the receptor, they dissociate and can
STEPS IN THE PROCESS OF CHEMICAL TRANSMISSION undergo to the following:
1) enzymatic degradation
1. Arrival of action potential in the presynaptic terminal initiates 2) re-uptake by presynaptic neuron
synaptic transmission 3) diffusion into the bloodstream
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Table below: neurotransmitters (NTs) and their function Table below summarizes the types of Adrenoreceptors
NTs Function Pathology • vasoconstriction
α1 • peripheral resistance
Enables muscle With Alzheimer’s Disease, • blood pressure
Acetylcholine action, learning Ach-producing neurons • inhibition of norepinephrine release
(Ach) and memory deteriorate α2 • inhibition of acetylcholine release
• inhibition of insulin release
Influences Excess dopamine receptor • tachycardia
movement, activity ® Schizophrenia
Dopamine • lipolysis
learning, attention, Starved of dopamine ® ß1
& emotion • myocardial contractility
Parkinson’s Disease • release of renin
Affects mood, Undersupply linked to • vasodilation
hunger, sleep and depression. Prozac and • slightly ¯ peripheral resistance
Serotonin arousal some other antidepressant ß2 • bronchodilation
drugs raise serotonin levels • muscle and liver glycogenolysis
• glucagon
Adrenoreceptors
• Metabotropic receptor
• Responds to catecholamines
POST SYNAPTIC POTENTIALS
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• Temporary depolarization of postsynaptic membrane caused
by the flow of positively charged ions into the post synaptic
1.05 Autonomic Nervous System
cell
SENSORY AND MOTOR NEURONS
Inhibitory Postsynaptic Potential (IPSP)
• Hyperpolarization and inhibitory response Table below: Sensory and Motor neuron
Sensory Neuron Motor Neuron
• Temporary hyperpolarization of postsynaptic membrane
caused by flow of [-] charged ions into postsynaptic cell a.k.a. Afferent Neuron Efferent Neuron
• ¯ neuron’s membrane potential and decreases the occurrence Pathway Ascending Pathway Descending Pathway
of an action potential. (from periphery to (from center to periphery
center)
SUMMATION Somatic Sense pain, Innervation to skeletal
temperature, pressure muscles
1. Temporal summation and touch
• The same presynaptic neuron stimulates the Autonomic Sense GI stretch reflex Innervation to smooth,
postsynaptic neuron multiple times in a brief period ® cardiac muscles and
glands.
depolarization ® action potential
2. Spatial summation
SOMATIC vs AUTONOMIC NERVOUS SYSTEMS
• Multiple neurons all stimulate postsynaptic neuron
resulting in a combination of EPSPs ® action potential Table below: Comparison of Somatic NS and ANS
Somatic NS ANS
SYNAPTIC INHIBITION
Activation Voluntary Involuntary
No. of 1 2
Presynaptic Inhibition
neurons in (spinal cord to muscle) (pre and post-ganglionic)
• ¯ EPSP due to ¯ NT release in presynaptic terminal pathway
• Mechanism Impulse Uninterrupted Interrupted with another
o GABA opens Cl- channels in excitatory presynaptic propagation synapse between pre-
terminal ® Cl- influx ® ¯ acting potential arriving at and post ganglia
knob ® ¯ Ca2+ influx ® ¯ NT released ® ¯ post-synaptic Nerve fibers Aα motor neuron B fibers for preganglion
response (¯ EPSP) C fibers for postganglion
Effector Skeletal muscles Smooth muscles, cardiac
Postsynaptic Inhibition organ muscles, and glands
• No threshold Effect of Always causes an Can either cause
• Occurs due to hyperpolarization of postsynaptic membrane impulse effect (muscular stimulation or inhibition
• membrane potential contraction)
• Can summate with no refractory period Number of 1 2
synapse (NMJ) Peripheral ganglia and
Presynaptic Facilitation Neuroeffector junction
• Nicotinic acetylcholine receptors control cation channel for (NEJ)
Ca2+
• Ca2+ influx ® NT release
AUTONOMIC NERVOUS SYSTEM
NEUROMUSCULAR JUNCTION
• Controls smooth muscles, cardiac muscles and glands.
• A chemical synapse connecting motor nerve and muscle • Maintains homeostasis and response coordination to external
fibers stimuli
• Acetylcholine serves as chemical neurotransmitter • Contain CNS and PNS components and Sensory and motor
• Nicotinic and cholinergic in nature components
• Local potential = end-plate potential • Divided into 3 divisions: Sympathetic ANS, Parasympathetic
ANS, and Enteric Nervous System
Conditions affecting NMJ
• Myasthenia Gravis Table below: Anatomical difference of Sympathetic and
o Autoimmune disease where antibodies deform Parasympathetic ANS
acetylcholine receptors ® acetylcholine can no longer Sympathetic Parasympathetic
bind ® muscle weakness Origin of Thoracolumbar Nerves Craniosacral Nerves
o Treatment: Tensilon preganglionic T1-T12, L1-2/3 CN III, VII, IX, X, S2-
§ Allows large acetylcholine accumulation in synaptic neurons 4
space Branching of Divergent Limited/Minimal
• Lambert-Eaton Syndrome neuron 1 pre: 20 post 1 pre:1 post (except
o Antibodies block the Ca2+ channel ® ¯ acetylcholine vagus nerve)
release ® no muscle contraction Location of Near spinal cord Within or near the
o Treated with immunosuppression ganglia (paravertebral and effector organ
prevertebral)
Length of Pre: SHORTER Pre: LONGER
ganglionic Post: LONGER Post: SHORTER
neuron fibers
Other Myelinated preganglionic Has no rami
neurons separate from communicans
the ventral root of the
spinal cord via white
rami communicans,
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which will then go to Physiological Differences
adjacent paravertebral • Dual Innervation: most viscera have this
ganglia to make the • Antagonistic Dual Innervation – Opposite effects on target
sympathetic chain organs.
o Sympathetic neurons – HR (through adrenergic
Some of those stimulation)
unmyelinated o Parasympathetic neurons – ¯ HR (through cholinergic
postganglionic axons stimulation)
leave the sympathetic
• Complementary Dual Innervation – Similar effects on target
chain and re-enter spinal
organs
nerves via gray rami
o Parasympathetic innervations on salivary gland: profuse
communicans
watery saliva
o Sympathetic innervations on salivary gland: Thick,
Neurochemical Differences
viscous secretion
• Sympathetic Division o Different consistency of secretion but both secretory in
o Noradrenergic transmitter nature.
o Major transmitter: norepinephrine • Exclusive Innervation by sympathetic nervous system
o Exception: neuroeffector junctions in sweat glands use o Adrenal medulla
acetylcholine o Sweat glands
• Parasympathetic Division o Blood vessels
o Cholinergic transmission o Adipose tissues (lipolysis)
o Major transmitter: acetylcholine o Arrector pili muscle
o Kidneys and JG apparatus
Table below: Adrenergic and Cholinergic Receptors
RECEPTOR LOCATION G-PROTEIN Pharmacologic Difference
Adrenergic
α1 Smooth Muscles Gq 1. Sympathetic Agents
α2 GI tract Gi a. Sympathomimetic agents: mimics effect of sympathetic
β1 Heart nervous system (SNS) by binding to adrenergic receptors
β2 Smooth Muscles Gs or release of NE/E.
β3 Fat tissue b. Sympatholytic agents: inhibit effect of SNS by blocking
Cholinergic adrenergic receptors or inhibition of NE/E release.
M1 CNS Gq 2. Parasympathetic Agents
M2 Heart Gi a. Parasympathomimetic agents:
M3 Smooth Muscle Gq cholinergic/cholinomimetic drugs which enhace
M4 CNS Gi parasympathetic activity by mimicking Acetylcholine
M5 Glands Gq effects on receptors.
b. Parasympatholytic agents: antimuscarinic drugs that
Nm/N1 NMJ/Skeletal Muscle -
inhibit effect of Acetylcholine on receptors.
Nn/N2 Autonomic Ganglia -
REFLEX ARC: COMPONENTS
Cholinergic receptors
• All preganglionic neurons 1. Sensory/Receptor Organs: generate receptor potential
• All parasympathetic postganglionic neurons 2. Afferent Neuron: sends local potential to center
• Sympathetic post-ganglionic neurons innervating sweat 3. Integrating Center: generates synaptic potential that will
glands and blood vessels in some skeletal muscle trigger action potential
• Produce vasodilatory effect 4. Efferent Neuron: transmits signal from center ® effector
organ
Deactivation of Norepinephrine and Acetylcholine 5. Effector Organ: appropriate effect occurs
1. Enzymatic Degradation
o by Acetylcholinesterase AUTONOMIC CONTROL CENTERES IN THE CNS
o Epinephrine and Norepinephrine degraded by COMT
and Monoamine Oxidase (MAO). 1. Hypothalamus
2. Reuptake (mostly NE) • Temperature regulation by thermoreceptors in the CNS,
3. Diffusion away from the NEJ/NMJ skin and viscera.
• Energy homeostasis by regulation of feeding and body
Functional Differences weight.
Table below: Physiological effect of ANS impulses to effector • Servomechanism (water intake regulation)
organs 2. Pons: Regulation of respiration (pneumotaxic center)
SYMPATHETIC DIVISION PARASYMPATHETIC 3. Midbrain: Micturition
DIVISION 3. Spinal Cord: controls some reflexes, defecation
Fight or Flight Response Rest and Digest 4. Limbic System: controls emotion
Catabolic Anabolic
Widespread effects Localized Effect
• NE and E secreted directly • Limited branching (except
in the blood stream vagus nerve)
• Divergence of preganglionic
neurons
Longer lasting effect Short-lived effects
Due to slow NE reuptake Due to fast enzymatic
breakdown of Ach by
Acetylcholinesterase
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Transverse (T) Tubules
1.06 Muscle Physiology I • Extensive tubular network invaginating the muscle fiber
• Carries the action potential from sarcolemma membrane to
SKELETAL MUSCLE ORGANIZATION
sarcomeres
• Contains DHPR
Figure below: organization of skeletal muscle from gross to
molecular Level (Guyton & Hall, 13th Ed. Pg 76)
Sarcoplasmic Reticulum
• Site of Ca2+ storage and release for excitation-contraction
coupling.
• Connects with T-tubules via the terminal cisternae
• Contains RYR, calsequestrin, and SERCA
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CLINICAL CORRELATION • Incomplete tetanus:
o Maximum tension reached but frequency is not fast
• Muscular dystrophy enough to summate
o Mutated dystrophin-glycoprotein complex, which o Muscle fibers partially relax between stimuli
connects actin filament to cell membrane • Complete tetanus:
o S/SX: severe muscle wasting, progressive muscle o Maximum tension with stimuli summated
weakness o Further stimulus frequency causes muscle to no longer
o X-linked disorder; affects males only relax ® leads to fatigue
• Malignant hyperthermia
o Due to mutated RYR FACTORS AFFECTING MUSCLE TENSION
o Some anesthetics may cause uncontrolled release of
Ca2+ from SR in susceptible individuals Length-Tension Relationship
o S/SX: rigidity, tachycardia, hyperventilation, and • Passive tension: developed by stretching the muscle to
uncontrolled rise in body temp. different lengths. This is low at ideal length.
• Active tension: the active force developed from the
1.07 Muscle Physiology II contraction of the muscle.
• Maximum tension: when there is maximum overlap of thick
SKELETAL MUSCLE FIBERS and thin filaments.
• Ideal length: where active isometric tension is maximal
Slow twitch Fast twitch • If muscle stretches or contracts beyond optimal length,
“One Slow Red Ox” “Two Fast White Sugar” tension generated will lower because of lower actin-myosin
Type IIA (FOG) - Type IIB (FG) interaction
Type I (SO)
Intermediate
Red Muscle Figure below: Graphical representation of Length-Tension
Red Muscle White Muscle Relationship (Guyton & Hall, 13th Ed. Pg 81)
(from myoglobin)
Small Fibers Large Fibers
More oxygen stores
More glycogen stores
(myoglobin)
Moderate Low Capillary
High capillary density
capillary density Density
Glycolytic +
Oxidative (more Glycolytic
Oxidative
resistant to (anaerobic) –
(aerobic)
fatigue than Type fatigues quickly
IIB)
Even less
More mitochondria Less mitochondria
mitochondria
Fatigue slowly Fatigue slowly Fatigue quickly
+2
High Ca pump capacity (SERCA) –
Moderate Ca+2 pump
can relax faster ® ready for another
capacity (SERCA)
twitch again
Sustained/prolonged force Bursts of strength
Myosin with long cycle Myosin with rapid cycling rates
time
Able to sustain tension for Strong tension but will decrease in
prolonged period of time strength after a short time due to
with minimal decrease in fatigue
strength Frequency of Action Potentials
• Greater contractile force occurs when a muscle is exposed to
ELEMENTS OF MUSCLE CONTRACTION faster stimuli or very frequent nerve signals
• Tetanus occurs when there is maximal contractions and a
Motor Unit fusion of twitches. This is caused by frequent stimulation will
• All muscle fibers in a motor unit contract simultaneously and lead to a higher amount of force until maximum tension is
they interdigitate to preserve direction of contraction reached.
• Motor units will less muscles per motor nerve are for fine
control or for fine reaction Number of Motor Units Stimulated
• More signals from the nervous system would lead to more
All or None Principle motor units stimulated
• Stimulating one part of the motor unit will stimulate the other • Size Principle reflects how smaller fibers are more excitable
parts of the motor unit and would require lower levels of force while large fibers have
the highest threshold and would require greater strength
CONTRACTION SUMMATION
Force-Velocity Relationship
• Single Twitch: single, rapid contraction and relaxation • Velocity of contraction would depend on amount of force the
• Temporal Summation: high frequency stimulus muscle must develop
o Stronger contraction when current is applied before • load = ¯ velocity
complete relaxation • 0 load = v0 = fastest velocity of contraction
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MUSCLE CONTRACTION Cardiac Muscle
Table below: differences and similarities between cardiac muscle
• Isotonic Contraction and skeletal muscle
o Load is constant – fixed afterload Differences Similarities with skeletal
o Muscle length changes while contracting muscle
o Concentric contraction = shortening Cardiac Muscle • Striated
o Eccentric contraction = lengthening • Involuntary • Sarcomere structure
• Shorter • T-tubules, SR
• Isometric Contraction • Branched • Actin, myosin,
o Muscle length (preload) is constant or fixed • Electrically linked troponin, tropomyosin
o Tension is measured (intercalated discs) that
o Elastic elements are the ones that change in length can contract as a unit
• Influx of Ca2+ through
MUSCLE FATIGUE DHPR triggers
calcium-induced
Central Fatigue calcium release from
• Caused by discomfort, lack of motivation or psychological RYR
factors. This precedes physiologic fatigue
• Can reflect changes in CNS and may involve altered input to
motor control centers of the brain and spinal cord - THE END -
Peripheral Fatigue
• Depletion of fuel = no more energy source
• Accummulation of lactic acid + phosphates
MUSCLE REMODELING
Hypertrophy
• muscle mass
• parallel (thickens) ® speed of muscle shortening
• series (lengthens) ® force generated by muscle cells
Atrophy
• ¯ muscle mass
• Can occur after denervation or after immobilization in a cast
Hyperplasia
• muscle fibers with no change in muscle mass
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