COLLEGE OF ALLIED MEDICAL PROFESSIONS

University of the Philippines Manila

Bachelor of Science in Physical Therapy Class of 2017

Physio 21 [02]: Neurophysiology 1 Dr. Darwin Dasig 20 Aug 2014

Topics  This divides into presynaptic

I. The Nervous system terminals, each of which ends in a
II. Resting membrane potential number of synaptic knobs/terminal
buttons or boutons.
III. Local potential
 Can be classified into unipolar,
IV. Action potential or Nerve impulse bipolar, or multipolar.
V. Synapse and Synaptic transmission
VI. Somatosensory system

I. THE NERVOUS SYSTEM

 It is used for:
 Control of the body.
 Integration
 Integrates all the systems in order to
maintain homeostasis
 It is Contralateral.
 It senses danger from the external
environment and reacts accordingly in the
other direction
 The right brain controls the left side of the
body and vice-versa
 It interacts with the internal and external
environment in order to maintain homeostasis.
 It is composed of the Brain, Brain stem, Spinal
cord, nerves and muscles.
 Brain
 Serves many different functions.
 It is comprised of Neurons.
 These are the functional part of the
brain.
 It has a Cell Body (Soma).
 Contains the nucleus.
 Metabolic center of the cell.
 Controls all the maintenance of
the neuron.
 It has several processes called
Dendrites which extend outward
and becomes a receptive area for
an adjacent axon.
 It also has a long process called an
Axon that originates from the Axon
Hillock.
 Action potentials / Conducted
impulses generate in the initial
segment of the axon.
 Axons can end either on another
neuron or into an effect organ.
 Neurons function via:
 Electrical signals
 Local potential
 Nerve impulse/Action Potential
 Chemical signals
 Synaptic transmission
 Works in an All/None Response
II. RESTING MEMBRANE POTENTIAL
 In order generate a potential difference across
the membrane of the cell, there are two
conditions that must be met.
 There is an unequal distribution of ions of
one or more species across the membrane
(Concentration gradient).
 The membrane must be permeable to one
or more ions.
 Permeability is provided by the
presence of channels that may be open
or closed via voltage gauge.

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 The resting membrane potential of any neuron
is usually -70mV.
 Plasma membrane
 Composed of Phospholipids.
 Phospholipids have polar head
(Hydrophilic) and 2 non-polar tails
comprised of fatty acyl chains
(Hydrophobic).
 They are amphiphatic.
 Can combine to form a circular shape
with the hydrophilic head on the
outside or into a more stable lipid
bilayer with the heads on the outside.
 This formation would not allow
charged/polar molecules to cross
the lipid bilayer.
 Structural proteins are present in
order to allow charged or large
particles to pass through.
 Small and non-charged particles
are the only ones able to pass
through this bilayer.
 The permeability of the membrane for ion
species (K+,Na+,Cl-) contribute to the charge
of the resting membrane potential.
 K+ ions are intracellular.
 Na+, Cl- ions are extracellular.
 No Na+ leak channels are present
(Voltage gauged only).
 K+ and Cl- can move freely through the
plasma membrane.
 Gibbs-Donnan Equilibrium
 “In the presence of a non-diffusible ion,
diffusible ions distribute themselves so that
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[02]: Neurophysiology 1
at equilibrium, their concentrations are
equal.”
 This is affected by the concentration and
electrical gradient.
 K+ and Cl- ions can move freely through the
membrane. But negatively charged
proteins that are present in the membrane
prevent Cl- ions from moving inward,
resulting in their extracellular nature.
 [K+]i = [Cl-]o
[K+]o [Cl-]i
 Donnan Effect
 Refers to the asymmetric distribution of
permeant ions at equilibrium.
 Electrical difference across the membrane
with magnitude is determined by Nernst
equation.
 Transmembrane Potassium Ion Gradient thru
Non-Gated Potassium Ion Leak Channels
 Nernst equation
 Diffusion Pressure
 Wd = RT (ln[C]hi – ln[C]lo)
 Electric Pressure
 We = (Em) (Zi) (F) Em=
absolute membrane potential; Zi =
valence (number of charges on the
ion); F = faraday (number of
coulombs per mol of ion)
 At equilibrium:
 There is no net movement.
 Diffusion pressure = Electrical
pressure.
 This is used to determine the
equilibrium potential of a single
diffusible ion (The potential dictates
the direction of the motion that the
ions follow to attain equilibrium).
 K+ = - 90 mV
 Moves outside via leak
channels.
 Na+ = + 60 mV
 Moves inward via gated
channels.
 Cl- = - 70 mV
 No net movement.
 In equilibrium with the RMP
* Leak channels allow free movement of the ion
* The Membrane potential at rest depends
primarily on the transmembrane potassium ion
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gradient thru non-gated potassium ion leak
channels
 K+ leak channels
 Open and closed voltage-gauged channels
 K+ ions can move freely but the RMP doesn’t
reach the equilibrium potential of K+ because
Na+ can move and leak In the membrane in
small quantities
 Na+ ions has no leak channels only voltage-
gauged channels are present
 Resting membrane potential via Goldman Constant
field equation
 This equation takes into account all the
permeabilities of the ions present in and out of
the cell.
 Takes into account the concentration ratios of
each of the ions.
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*K+ moves out freely allow the RMP to move to -90mV while
Na+ ions move inward in small quantities to revert the RMP
back to -70mV.
 Na+-K+ ATPase pump
 Converts ATP to ADP and P to actively transport 3
Na+ ions out and 2 K+ ions in which results in a net
loss of +1 charge inside the cell.
 This maintains the difference in concentration of
Na+ and K+ and the negativity of the inside of the
cell.
 Most important part of the RMP.
 The asymmetry of the concentrations results in
the electric charge.
 The resting membrane potential is not in equilibrium.
 The RMP is only a steady state due to the presence
of the ATPase pump.
 Due to the usage of ATP (Equilibrium doesn’t need
energy in order to be maintained).
III. LOCAL POTENTIAL
 Local Potential
 Transient shift of the membrane potential
in a localized area of the cell (quick
change).
 Change in one portion of the membrane
(any kind of change).
 Lygan change – a neurotransmitter
combines with receptor that opens
(synaptic potential).
 Graded response – amplitude is
proportional to size of stimulus (more to
more).
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 Hyperpolarization ↔ depolarization  Describes the distance of the voltage change along

(hyper = increase negativity) the membrane.
 Rapid ↔ long  Distance at which the initial transmembrane
voltage change has fallen to 37% of its peak value.
 The larger the space constant, the farther along
the membrane a voltage change is observed after
a stimulus is applied.
 Limit of the local potential (distance away the
body).

Rm = transmembrane resistance (ohm-cm)

Ra = internal axoplasmic resistance (ohm/cm)

↑ Diameter of axon or dendrite

• ↓ Ra (internal axoplasmic resistance)
• ↑ space constant
• ↑ current will flow farther along cell
 Local Potential Kickoff ↑ Rm (transmembrane resistance)
 Local change in permeability of the membrane to 1 • ↑ space constant
or more ions. • less current leaks out
 Synaptic potential  Directly related to the transmembrane resistance.
 Lygan change  High transmembrane resistance – longer
 Generator potential distance (how easy to leave; barrier will
 chemical change squish them out).
 Change in voltage/current applied from a source.  Low Internal axoplasmic resistance – high
 Electrotonic potential distance (how easy to travel; inside is very
 Add voltage spacious).
 *increase Na and K conductance =
depolarization due to high driving force of  Local Potentials CAN BE SUMMATED!
Na (lesser degree when increased Na  Spatial summation
conductance).  Add up beside each other (through space).
 Local Potentials  Remain localized in region where stimulus is
 Change in potential develops and subsides over a applied.
few milliseconds.  Not sharply confined: falls off over a finite
 Remain localized in region where stimulus is distance on the membrane.
applied.  Temporal summation
 Not sharply confined: falls off over a finite distance  Change in potential develops and subsides
on the membrane. over a few milliseconds.
 Within milliseconds and within a single area.  Same space (through time)
Voltage change = current X resistance  Repeated stimulation
 Some ions leak out across membrane.
• Lesser charges reach more distant
sites.
• stable resistance : decreased current
→ decreased voltage
 Local potential (Voltage change) – decreases
with distance from the point of stimulation
 Space constant

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 An action potential is propagated with the

same shape and size along the entire
*Spatial summation (top) and temporal summation length of an axon.
(bottom)  Action potentials are usually initiated at the
*summated subthreshold potentials may reach axon hillock of the axon.
threshold and produce an action potential  The action potential is the basis of the
*neurons = electrical and chemical communication
signal- carrying ability of nerve cells.
IV. Action potential or Nerve impulse  The patterns of conducted action
 ACTION POTENTIAL potentials encode the information
 Fleeting, self-renewing wave of membrane conveyed by nerve cells.
depolarization that propagates without
decrement along the length of a nerve
axon at high speed.
 Is a rapid, all-or-none change in the
membrane potential followed by a return
to the resting membrane potential.

 Spike Potential
 Sharp rise and rapid fall of the membrane
potential.

 Voltage-dependent ion (Na+ and K+)

channels in the plasma membrane are the
basis for action potentials.

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 After-depolarization
 Slower fall at end of spike potential.
 supernormal period
 After-hyperpolarization
 Overshooting of membrane repolarization after
reaching resting level.
 subnormal period
 All or None Law
 Full-pledged AP produced once threshold intensity
is reached.
 Further increase in intensity of stimulus does not
produce increment or other change in AP.
 No AP if stimulus is subthreshold in magnitude.
 Constant amplitude and form.

 Refractory Period
 Absolute
 Threshold to one-third of repolarization.
 No stimulus will excite the nerve.
 Relative
 Up to start of after-depolarization.
 Stronger than normal stimulus can cause
excitation.

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 ↓ effective capacitance of axonal

membrane: ↑distance between ICF & ECF
 ↓ time constant
 ↑ conduction velocity
 unmyelinated axons
 Voltage gated Na+ and K+ ion channels
distributed uniformly along length of
axonal membrane.
 myelinated axons
 High concentration of voltage-gated Na+ and
K+ ion channels in axon hillock & nodes of
Ranvier.
 Speed of Action Potential Propagation  low density along internode
 diameter of axon

*↑ diameter → ↓cytoplasmic resistance → ↑ flow of

ions → ↑length of axon depolarized (↑space constant)
→ ↓time needed for AP to travel along axon

 Saltatory Conduction
 Myelinated axons
 myelinated: axons > 1μm diameter
 conduction velocities:myelinated = 3 – 120
m/sec; unmyelinated = 0.5 – 2.0 m/sec

 myelin
 ↑ effective resistance of axonal membrane
(transmembrane resistance Rm): ions must
flow through myelin before reaching ECF
 ↑ space constant

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V. SYNAPSE AND SYNAPTIC TRANSMISSION  They are capable of amplifying or inhibiting

 Synapse - A junction where the axon or some other signals.
portion of one neuron (called the presynaptic  They can transmit information over a broad
neuron) terminates on the dendrites, soma, or axon time domain.
of another neuron (called the postsynaptic neuron),  They exhibit Plasticity.
muscle cell, or gland cell.  Refers to the synaptic strength function of
 Types of Synapses recent neural activity.
 Electrical  It plays a role in learning and memory.
 There is a gap junction formed between the  Essential to the success of the vertebrate
presynaptic and postsynaptic neuron. species.
 There is cytoplasmic continuity.
 Since the neurons are connected to each
other, they are inflexible (they cannot form
new connections).
 Each gap junction is formed by two
hemichannels called Connexons, one
contributed by each cell.
 The gap junction forms low-resistance
bridges through which ions pass with relative
ease.
 There is very little distance between the
two neurons (3nm-5nm).
 Ionic currents travel extremely fast
through these bridges.
 There is no synaptic delay.
 The structure allows for the bidirectional  Kinds of Synapses Based on Location
travel of the ionic currents.  Inhibitory synapses – nearer to the axon hillock
 Uses very little metabolic energy and  Axo-somatic (axon to the soma) – most
molecular machinery. inhibitory
 Highly reliable.  Excitatory synapses – near the dendrites
 Axo-dendritic (axon to a dendrite) – most
 Chemical excitatory
 Presynaptic and postsynaptic neurons are  Axo-axonal (axon to another axon)
separated by a space called the Synaptic Cleft.  Dendro-dendritic (a dendrite to another dendrite;
 There is no cytoplasmic continuity. rare)
 Since the neurons are separated from  Soma-somatic (the soma to another soma; rare)
each other, they are flexible (they can  Dendro-somatic (a dendrite to a soma)
form new connections as required, such as
when learning new skills or remembering
something). This is termed “Plasticity.”
 The presynaptic neuron uses chemical
transmitters called Neurotransmitters
that bind to the postsynaptic neuron to
propagate potentials.
 Neurotransmitters are able to travel much
larger distances (30nm-50nm) between
the presynaptic and postsynaptic neuron.
 The neurotransmitter is unidirectional:
from the presynaptic neuron to the
postsynaptic neuron.

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 The neurotransmitters inside the

synaptic vesicles are then released to
the synaptic cleft via exocytosis.

 Various Structures Involved

 Synaptotagmin
 The synaptic vesicle’s Ca2+sensor.
 Neurotransmitters  It binds proteins that cause the
 Stored in synaptic vesicles. vesicles to dock and bind to the
 Released into the synaptic cleft with the nerve presynaptic terminal membrane.
impulse.  SNAREs
 Act on appropriate receptors on the  These are tethers employed by the
postsynaptic membrane. synaptic vesicle and the presynaptic
 Different Neurotransmitters neuron’s cell membrane to ensure
 Small-molecule transmitters that the vesicle reaches the cell
 Monoamines (Acetylcholine, Serotonin, membrane.
Histamine)  Vesicle SNARE (v-SNARE)
 Catecholamines (Dopamine,  Synaptobrevin
Epinephrine, Norepinephrine)  Terminal membrane SNARE (t-
 Amino Acids (Glutamate, GABA, Glycine) SNARE)
 Large-Molecule transmitters
 Syntaxin
 Neuropeptides (Substance P,
 SNAP-25
Enkephalin, Vasopressin)
 Snare Mechanism
 Glutamate – The main excitatory transmitter.
 Initial State
 GABA (Gamma-Aminobutyric Acid) – The main
 The vesicle moves to the nerve
inhibitory transmitter.
terminal membrane, which contains
 Neuromodulators
Syntaxin and SNAP-25 (t-SNAREs).
 Chemicals released by neurons with little or no
 Formation of the Ternary Complex of
direct effects on their own, but can modify the
Snares
effects of neurotransmitters.
 N-sec-1 (a protein in Syntaxin),
 Transmitter Release
dissociates from Syntaxin.
 Mechanism
 This allows the Syntaxin and
 The action potential opens voltage-
the SNAP-25 to form a complex.
gated Ca2+ channels at the end of the
axon.  The distal end of the
 The axon allows Ca2+to enter. Synaptobrevin begins to wind
 This increases the Ca2+intracellular around the Syntaxin-SNAP-25
concentration. complex. This results in a
 The increased Ca2+ level triggers the ternary complex.
binding of synaptic vesicles to the  Tightening of the Ternary Snare Complex
membrane.  The three SNAREs continue to form
a tight bundle of helices.

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 UPM PT 2017 Physio 21
 The vesicle is further drawn to the
presynaptic membrane.
 Fusion and Exocytosis
 The entry of Ca2+ via voltage-gated
channels causes an influx of Calcium
that binds to Synaptotagmin.
 This triggers fusion of the vesicle
and the cell membrane, and
consequent exocytosis of the
neurotransmitter.
 Disassembly of the Ternary Snare
Complex
 α-SNAP and the ATPase NSF bind to
the ternary SNARE complex.
 They use the energy of ATP
hydrolysis to disassemble the
SNAREs.
 Recycling of Snares
 The vesicle is endocytosed, and the
three SNAREs are again ready for
use.
 Additional Information
 Transmitter release is a quantum.
 The number of neurotransmitter
molecules released by one vesicle is
fixed.
 Even if the neurotransmitters are
quantized (Quantum Content), the
number of quanta released when the
synapse is activated depends on the
level of Ca2+.
 The greater the Ca2+, the more
quantized neurotransmitters are
released.
 Burst of transmission terminates with
rapid sequestration in organelles (such
as the mitochondria) within the ending.
 Ca2+is extruded via the Na+- Ca2+Antiport.
 Neurotransmitter Receptors
 Ionotropic Receptors
 The chemical receptor is also the
channel.
 Ligand-gated ion channel proteins
 Rapid opening of ion channels
 Depolarization and hyperpolarization
 Nicotinic Acetylcholine, GABA, Glycine,
Serotonin, Glutamate
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 Metabotropic Receptors
 The chemical receptor is not the
channel.
 The cell membrane uses proteins to
facilitate the channeling of the
neurotransmitter.
 Seven-transmembrane-helix-receptors
 G protein-linked
 G proteins are nucleotide regulatory
proteins that bind GTP.
 Ion channel proteins or 2nd messenger
effector proteins
 Translate signals to biological
effects inside the cell.
 Glutamate, Muscarinic Acetylcholine, α
and β adrenergic
 Excitatory Postsynaptic Potential (EPSP)
 Local potential of depolarization under the
active zone from a single stimulus.
 Increases the excitability of the neuron to other
stimuli.
 Ionic basis:
 Na+ channels are opened.
 There is an increase in Na+ conductance
through ligand-gated channels.
 Closure of K+ channels.
 Inhibitory Postsynaptic Potentials (IPSP)
 Local potential of hyperpolarization
 Postsynaptic direct inhibition.
 Stimulation to other stimuli is decreased.
 Ionic basis:
 Opening of CI- channels.
 There is an increase in Cl- conductance
causing an outward flow of current.
 Opening of K+ channels.
 Closure of Na+ or Ca2+ channels.
 Excitation
 Spatial and Temporal summation.
 Spatial summation refers to excitation
over an area, where intersecting areas
of excitation in the postsynaptic neuron
are added-up.
 Temporal summation refers to repeated
excitation over time.
 The axon hillock is the area of highest
integration
 Inhibition
 Presynaptic Inhibition
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 Provides a mechanism for controlling

the efficacy of transmission at individual
synapses.
 Mediated by Axo-axonal synapses.
 Postsynaptic Inhibition
 Direct Inhibition
 Inhibition with IPSP
 Not a consequence of previous
discharges of the postsynaptic
neuron.
 Indirect Inhibition
 Due to the effects of previous  Convergence:
postsynaptic neuron discharge  Many to one – Many presynaptic
(refractory period or during after- neurons converge on a single
hyperpolarization). postsynaptic neuron.
 Long-term Potentiation
 Characterized by the enhanced transmission at
synapses that follow high frequency
stimulations.
 First observed in the hippocampus, a
part of the brain that plays an important
role in memory.
 Depends on the presence of NMDA (N-methyl-D-
aspartate) receptors in the postsynaptic
membrane.
 Plays a role in memory and associative learning.
 Convergence and Divergence
 One to one.
 Divergence:
 One to many – The axon of the
presynaptic neuron divides into many
branches that end on many
postsynaptic neurons.
 Spatially focused – The branching is
much less, usually confined to several
effectors in close proximity.
 Widely divergent – The branching goes
over a wide area.

REFERENCES:

Barret, K.E., Barman, S.M., Biotano, S., & company. (2012).

Ganong’s Review of Medical Physiology, 24th ed. The McGraw-
Hill Companies, Inc., United States of America.

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Dasig, D. (2014). CAMP Physio 21 Neurophysiology 1 2014

Power point presentation.

Koeppen, B.M., Stanton, B.A. (2012). Berne and Levy

Physiology, 6th ed. Molsby Inc., Elsevier Inc.

Waxman, S.G. (2013). Clinical Neuroanatomy, 27thed. The

McGraw-Hill Companies, Inc., United States of America.

Authors’ Notes on the Subject Matter

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