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Excitable tissues

Outline
• Excitable tissues
• Morphology of the nerve cell
• Functional organization of neurons
• Membrane potentials
• Excitation & conduction along the nerve
• Nerve types & functions
• Muscles
• Communication in excitable tissues
Excitable tissues
• Excitable Tissues = electrically active tissues
– Nervous tissue
– Muscle
• All cells have electrical properties
• In the resting state, these properties are due to the
electrical properties of the phospholipid bilayer.
– The hydrophobic core of the phospholipid bilayer is an
insulator.
• Electrical charge does not flow freely across a bilayer.
• An electrical gradient can exist across the membrane; the inside
of a cell can have a different voltage (electrical potential) than the
outside of a cell.
Excitable tissues
• An excitable cell reacts to stimuli by altering
its membrane characteristics
• Two types
– Nerve cells:- Transmit and modify impulses within
the nervous system
– Muscle cells:- Contract either in response to nerve
stimuli or autonomously
Nerve cells (the neuron)
• Basic structural and functional units of the nervous
system.
– Cannot divide by mitosis.
• Respond to physical and chemical stimuli.
• Produce and conduct electrochemical impulses.
• Release chemical regulators (neurotransmitters)
• Integrate and transmision of nerve impulses
• Nerve:
– Bundle of axons located outside CNS.
• Most composed of both motor and sensory fibers.
Basic structure of the neuron
NERVE CELL:
• The neurons are the basic
building blocks of the nervous
system, their axons may or
may not be myelinated
• The myelin sheath is produced
by the Schwan cells. It
envelops the axon except at
the ends & the nodes of
Ranvier
• The impulse is conducted
faster in myelinated than
unmyelinated nerves.
The Nerve cell
• Cell body (perikaryon):
– “Nutrition center”
– Cell bodies within CNS clustered into nuclei, and in PNS in ganglia
• Dendrites:
– Provide receptive area
– Transmit electrical impulses to cell body
• Axon:
– Conducts impulses away from cell body
Neurons
Schwann cells
• Provide insulation to
axons
• Increase conduction
velocities of the axons
(saltatory conduction)
• One Schwann cell can
provide myelin to over
ten axons
Functional Classification of Neurons

• Based upon direction


impulses conducted.
• Sensory or afferent:
– Conduct impulses from
sensory receptors into
CNS.
• Motor or efferent:
– Conduct impulses out of
CNS to effector organs.
• Association or
interneurons:
– Located entirely within the
CNS.
– Serve an integrative
function.
Structural Classification of Neurons
• Based on the number of
processes that extend
from cell body.
– Unipolar:
• One pole with both axon
and dendrites (only found
in embryonic life)
– Pseudounipolar:
• Short single process that
branches like a T
– Sensory neurons
– Bipolar neurons:
• Have 2 processes.
– Retina of the eye
– Multipolar:
• Have several dendrites and
1 axon.
– Motor neuron
Classification depending on the axon length

• Golgi type I:
– Long axons; cell bodies in the central nervous
system and axons move to the peripheral organs
• Golgi type II:
– Short axons; found in the cerebral cortex and
spinal cord
Special Properties of Neurons
• Excitability--Action Potential in Axons
• Conduction--Action Potential in Axons
• Transmission--Synapses, Electrical & Chemical
• Integration--Postsynaptic Cell
• Plasticity—Able to change in form and
environment in response to alternations in
environment
Resting Membrane Potential
Definition: it is the potential difference recorded across the
cell membrane at rest
Causes:
• 80% caused by selective permeability of the cell
membrane
The K+ diffuses out the cell & Na+ diffuses inside the cell
according to concentration gradient.
The K+ permeability is 50-75 folds more than Na+
• 20% is caused by the Na+ - K+ pump an active process
that needs energy taken from ATP. This is very important
to maintain the concentration gradient across the cell
membrane
Resting Membrane Potential (Vr)
Membrane Potential
• The membrane potential is the difference in
electrical potential (voltage) between the
inside and outside membrane surfaces under
resting conditions
• Cells have an excess of negative charges at the
inside surface of the cell membrane and
exhibit a negative membrane potential at rest
Potentials
• All potentials result from ions moving across
membranes.
• Two forces on ions: Diffusion (from high to low
concentration); Electrical (toward opposite charge
and away from like charge).
• K+ make - potentials; Na+ make + potentials.
Resting Potential Results from Passive K+
Channels and EK+

• At rest, membrane potential is -60 to -70 mV


in most neurons. Why?
• K+ is most permeable, due to leak of K+
through passive K+ channels.
• Therefore, K+ ions leave, making the inside
more negative.
A cell is
“polarized”
because the
interior (ICF)
side of the
membrane
is relatively
more
negative
The membrane potential is due to the
than the
sodium ions found in the extracellular
exterior
matrix and the potassium ions found in
(ECF). the intracellular matrix
Widmaier, et al., 2006
Membrane potentials
• Membrane potentials are due to the
• Diffusion of ions down their concentration gradients
• The electric charge of the ion
• Any membrane pumps for that ion

• Influx is the net movement of ions into the


cell from the ECF.
• Efflux is the net movement of ions out of the
cell to the ECF.
• Flux (the movement of charges) is always
measured in millivolts (mV).
Factors contributing to RMP (Vr)
1. Because the K+ concentration inside the cell
is higher than the outside concentration, K+
moves out of the cell, leaving excess negative
charges on the inside of the cell membrane
2. The Na+/K+ pump acts as a second factor to
generate negative charges on the inner
membrane surface by pumping three Na+ out
and only two K+ in. This leaves a net positive
charge on the outside of the cell.
3. The K+ efflux is primarily responsible for the
resting membrane potential
• The RMP is established by different
permeabilities or conductances of permeable
ions
• RMP of nerve cells is more permeable to K+ than
to Na+
• Changes in ion conductance alter currents, which
change the membrane potential
• Hyperpolarization is an increase in membrane
potential in which the inside of the cell becomes
more negative
• Depolarization is a decrease in membrane
potential in which the inside of the cell becomes
more positive
Concentration of Ions and State of Channels at Rest

-65 mV

Concentrations maintained by Na+/K+ and Ca++ pumps.


Equilibrium potential
• The equilibrium potential is the membrane
potential that exists if the cell membrane
becomes selectively permeable for an ion,
causing the distribution of the ion across the
membrane to be at equilibrium
Action Potentials
• An action potential is a rapid, large decrease in
membrane potential
• Action potentials usually occur because of increases
in the conductance of Na+, Ca2+, and K+ ions
• Threshold is the membrane potential that induces an
increase in Na+ conductance to produce an action
potential
• Depolarization produces an opening of the Na+
channel through fast opening of the activation gates
and slow closing of the inactivation gates
Action Potentials
Membrane Permeabilites

• AP is produced by
an increase in Na+
permeability.
• After short delay,
increase in K+
permeability.
Resting and Action Potentials
Properties of Action Potentials
– "All or none"
• Generation of an action potential is determined solely
by the ability of the stimulus to cause the cell to reach
threshold
• If the threshold potential is reached, an action
potential is generated; if it is not reached, no action
potential is generated
• Regardless of stimulus intensity or energy content,
the action potential will have the same amplitude
– Frequency
• Increasing stimulus intensity increases the frequency
of action potential generation.
Properties of Action Potentials
– Refractory periods
• During refractory periods, the cell is unable to generate an action
potential.
• Prevent tetany
• Absolute refractory period
– An action potential cannot be generated, regardless of stimulus intensity.
– This occurs during the depolarization phase of the action potential and is
due to closure of the sodium channel inactivation gates
• Relative refractory period
– Only a stimulus with intensity much greater than threshold can stimulate
another action potential
– This occurs during the repolarization phase and is due to the inactivated
conformation of the voltage-gated sodium channels
– The conductance of K+ is higher than in the resting state, so the
membrane potential becomes more negative. Relative refractory period:
only much larger than normal stimulus intensity can generate an action
potential; occurs during repolarization phase
Refractory Periods

• Absolute refractory
period:
– Axon membrane is
incapable of producing
another AP.
• Relative refractory period:
– VG ion channel shape alters
at the molecular level.
– VG K+ channels are open.
– Axon membrane can
produce another action
potential, but requires
stronger stimulus.
Propagation of action potentials
• Propagation of the action potential requires a
system that regenerates the action potential
along the axon
• Conduction velocity is increased by increased
fiber size and myelination
– Dependent on the magnitude of the depolarizing
current
• Myelinated nerves exhibit saltatory conduction in
which the action potential skips from node to
node where the voltage-gated Na+ channels
congregate
Conduction in an Unmyelinated Axon

• Cable spread of
depolarization with influx
of Na+ depolarizes the
adjacent region
membrane, propagating
the AP.
• Conduction rate is slow.
– AP must be produced at
every fraction of
micrometer.
• Occurs in 1 direction;
previous region is in its
refractory period.
Conduction in Myelinated Axon

• Myelin prevents movement of


Na+ and K+ through the
membrane.
• Interruption in myelin (Nodes
of Ranvier) contain VG Na+
and K+ channels.
• AP occurs only at the nodes.
– AP at 1 node depolarizes
membrane to reach
threshold at next node.
• Saltatory conduction (leaps).
– Fast rate of conduction.
Communication in excitable tissues

• Synapses
–Chemical
–Electrical
• Neuro-muscular junction (NMJ)
The Synapse
• Functional connection between a neuron and another
neuron or effector cell.
• Transmission in one direction only.
• Axon of first (presynaptic) to second (postsynaptic)
neuron
• Synaptic transmission is through a chemical gated
channel
• Presynaptic terminal (bouton) releases a
neurotransmitter (NT)
Synaptic transmission
Physiologic anatomy of the synapse (from Guyton & Hall)
Classification of synapses
• Anatomical
– Axosomatic (axon to soma/ cell body)
– Axodendritic (axon to dendrtie)
– Axoaxonal (axon to axon)
• Functional
– Electrical synapse
» Continuity provided by gap junctions between the two neurons
» Minimal delay, bidirctional
» E.g. cardiac muscle, intestinal smooth muscle, epithelial cells of the eye lens
– Chemical
» Signal transmitted by release of a chemical transmitter
» No continuity between the pre and post synaptic neurons
Types of synapses
Electrical Synapse

• Impulses can be
regenerated without
interruption in adjacent
cells.
• Gap junctions:
– Adjacent cells electrically
coupled through a channel.
– Each gap junction is
composed of 12 connexin
proteins.
• Examples:
– Smooth and cardiac
muscles, brain, and glial
cells.
The Chemical Synapse

• Terminal bouton is
separated from
postsynaptic cell by
synaptic cleft
• NTs are released from
synaptic vesicles
• Vesicles fuse with axon
membrane and NT
released by exocytosis
• Amount of NTs released
depends upon frequency
of AP
Synaptic Transmission

• NT release is rapid because many vesicles form


fusion-complexes at “docking site.”
• AP travels down axon to bouton.
• VG Ca2+ channels open.
– Ca2+ enters bouton down concentration gradient.
– Inward diffusion triggers rapid fusion of synaptic
vesicles and release of NTs.
• Ca2+ activates calmodulin, which activates protein
kinase.
• Protein kinase phosphorylates synapsins.
– Synapsins aid in the fusion of synaptic vesicles.
Synaptic Transmission
• NTs are released and diffuse across synaptic
cleft.
• NT (ligand) binds to specific receptor proteins
in postsynaptic cell membrane.
• Chemically-regulated gated ion channels
open.
– EPSP: depolarization.
– IPSP: hyperpolarization.
• Neurotransmitter inactivated to end
transmission.
Chemical Synapses

• EPSP (excitatory
postsynaptic
potential):
– Depolarization.
• IPSP (inhibitory
postsynaptic
potential):
– Hyperpolarization
The neuromuscular junction
• Motor end plate
• Composed of
– Presynaptic motor neuron; Synaptic cleft; Postsynaptic
membrane
The Neuromuscular juction
• The nerve fiber forms a complex of branching
nerve terminals that invaginate into the
surface of the muscle fiber but lie outside the
muscle fiber plasma membrane
• The entire structure is called the motor end
plate
• It is covered by one or more Schwann cells
that insulate it from the surrounding fluids
Neurotransmitter
• Signal transmission controlled by a
neurotrasmitter
• Acetylcholine is the neurotransmitter at the
NMJ
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