05. Exitable tissues.pptx it is important

Physiology of Excitable Tissues
Nerve
Muscle

Excitable Tissues
• Tissues capable of generation and transmission of
electrochemical impulses along the membrane.
E.g. nerve and muscle
Membrane potential:- A potential difference across all cell
membranes.
Inside is negative with respect to the outside.
• Excitable tissues have the ability to produce rapid, transient
changes in their membrane potential when excited.
• These brief fluctuations in potential serve as electrical signals

Resting membrane potential
• The electrical potential across the cell in a resting state.
• Can be recorded across the plasma membrane of living cells.
• Neurons are also highly polarized
• Excitable tissues have more negative RMP: - 70 mV to - 90
mV

Resting membrane potential
• The potential of unstimulated muscle and nerve cells, or
resting potential, amounts to – 50 to – 100mV
• The RMP of large nerve fibers when not transmitting nerve
signals is about –70 mv,
i.e the potential inside the fiber is 70 mVs more negative than the
potential in the ECF on the outside of the fiber.

Causes of RMP
1. ECF = very high Na+
while
the ICF = very high K+
.
2. The electrogenic nature of the
Na+
/K+
pump.
3. There are protein anions (i.e.,
negatively charged proteins)
within the ICF that cannot
travel through the PM.

Concentration and permeability of ions responsible for
membrane potential in a resting nerve cell

• Equilibrium potential:- membrane potential which puts an ion
in electrochemical equilibrium.
• Nernst equation determines this potential:
• where EMF is electromotive force and z is the electrical charge
of the ion (e.g., +1 for K+).
 Equilibrium potential for K+ (EK+) = -90
 Equilibrium potential for Na+ (ENa+) = +60

Ion Channels
• Ions diffuse across the membrane via ion channels.
1. Ungated (Leak) Ion Channel
Always open.
Direction of ion movement depends on electrochemical forces.
Important for determining RMP of a cell.
2. Gated channels:
Have gates that open or close due to change in the
conformation of the protein that forms the channel.

Types of gated channels
a. Voltage-gated channels:
 Open or close in response to changes in membrane potential.
b. Ligand-Gated Ion Channel
 State of the channel (open or closed) is influenced by the binding of a
ligand to the receptor.
c. Mechanically gated channels:
 Respond to stretching or other mechanical deformation
d. Thermally gated channels:
 Respond to local changes in temperature (heat or cold)

Changes in Membrane Potential
• Polarization: the inside of the cell is slightly –ve relative to the
outside
• Depolarization: membrane becomes less polarized; the inside
becomes less -ve than at resting potential
• Repolarization: membrane returns to resting potential after
having been depolarized
• Hyperpolarization: membrane becomes more polarized; the
inside becomes more negative than at resting potential

Cellular component of NS
• Two principal cell types that make up the NS:-
A. Neurons
Functional units of the NS.
Specialized for generation and transmission of nerve impulse.
B. Neuroglial cells
Supporting cells.
10-20x outnumber neurons.
Can multiply after maturation.

Structures of neurons
• Consists of 4 basic parts
1. Cell body
2. Dendrites
3. Axons
4. Axon terminals

Cell body (soma)
• The house of nucleus + organelles.
• The metabolic and trophic center of the neuron.
• Site of synthesis for proteins & other macromolecules.
• Reception + integration of input signals.
Dendrites
• Short processes (extensions) arise from the cell body.
• Receive signals from other neurons.

Axons (Nerve fibers)
• A single, elongated, tubular extension.
• Conduct action potentials away from the cell body →
conducting zone.
• Initiation of action potential at the axon hillock.
Axon terminals
• Highly branched ending of axon.
• Synthesis & release neurotransmitters in to the synaptic cleft by
exocytosis → output zone.

Classification of neurons
A. On the basis of function
1. Sensory neurons (afferent neurons)
• Transmit information into the CNS from receptors at their
peripheral endings.
2. Motor neurons (= efferent neurons)
• Transmit information out of the CNS to effectors (neurons,
muscles or glands).
3. Interneurons
• Integrate groups of afferent & efferent neurons into reflex
circuits.
• Lie entirely within CNS.
• Account for 99% of all neurons

B. On the basis of number of processes
1. Unipolar/monopolar neurons
• Have a single primary process
• Different segments serve as receptive/releasing terminals.
• At autonomic nervous system
2. Bipolar neurons
• Two processes (axon + dendrites)
• At sensory cells of retina, auditory, vestibular, olfactory
3. Multipolar neurons
• Single axon + many dendrites.
• Predominant type.

05. Exitable tissues.pptx it is important

Neuroglia (Glial cells)
• Not directly involved in signal processing.
• Morphologically different from the neurons (no axon +
dendrites).

Types:-
1. Peripheral neuroglia
a. Schwann cells
 Form myelin sheaths around peripheral axons.
• Insulation → speeds transmission of signals along
nerves.
b. Satellite cells
Encapsulate dorsal root + cranial nerve ganglia.

2. Central neuroglia
a) Astrocytes/Astroglia
 Regulate the external environment of neurons in the CNS.
 Providing structural and nutritive support to the brain.
 Re-uptake of neurotransmitters.
 Induce formation of the Blood-Brain Barrier.
b) Oligodendrocytes
 Form myelin sheaths around axons of the CNS.

c) Microglia
Immune cells of CNS.
Scavenging: removing debris after infection, injury or
neuronal death.
d) Ependymal cells
Form the epithelium that separates CNS from CSF.
Assist in the production & circulation of CSF within the
brain and central canal of the spinal cord.

Neural signaling
• Electrical signals are produced by changes in ion movement across the
plasma membrane.
• Membrane potential changes are the basis of signaling in the NS.
• Membrane potential is electrical energy difference between the inside
and outside of the cell.
• Resting membrane potential(RPM):-
 Steady transmembrane potential of a cell that is not producing an
electrical signal.
 -70 mV for typical nerve cell.

• Two forms of electrical signals:
A. Graded potential
Local changes in membrane potential.
Features:
• Depolarizing or hyperpolarizing.
• Variable in amplitude and duration.
• Conducted decrementally.
• Can be summed.
• Has no threshold and refractory period.
• Propagation is passive.

B. Action Potential
• Rapid, transient, self-propagating electrical excitation in the
plasma membrane of excitable cells.
• Features:
All-or-none phenomenon.
Always depolarizing.
Amplitude and duration is constant.
Nondecremental.
Has threshold and refractory period.
Propagation is active.

Refractory period
• An interval during which it is more difficult to elicit an AP.
• Voltage and time-dependent nature of gating particles.
A. Absolute refractory period
• Another AP can not be elicited, regardless of strength of
stimulus.
• Begins at the start of upstroke and extends into downstroke.
B. Relative refractory period
• A second AP can be elicited if the stimulus is adequate.
• Stimulus must be greater than normal (suprathreshold).

Propagation of Action Potential
Types:
1. Contiguous conduction
Occur in unmyelinated fibers.
AP generates at all sections of cell membrane.
2. Saltatory conduction
Occurs in myelinated fibers.
Nodes of Ranvier- impulse jumps from node to node.
More rapid than contiguous.

Saltatory conduction
Contiguous conduction

Factors affecting propagation
• Type of fiber
Velocity in myelinated nerve > nonmyelinated nerve.
• Axon diameter
Velocity ~ diameter of the fiber (↑SA, ↓R).
• Temperature
↓o
C → ↓ rate of change of permeability.

Stimulus (physical, mechanical, chemical, electrical…)

Sensory receptors

Transform stimulus energy/Transduction

Ion channels open

Inward flow of current (Na+
, K+
)

Depolarization  ΔEm

Receptor potential/Generator potential

Action Potential

Conduction and effect
Mechanism of signaling

Synaptic transmission
•Communication among neurons, with muscles and glands.
Synapse
• A site at which an impulse is transmitted from one cell to
another.
• An average neuron forms about 103
synaptic connections.
• Components:
1. Terminals of presynaptic axon
2. Receptor on the postsynaptic cell
3. Zone of apposition/synaptic cleft

The components of a chemical synapse

• There are 2 types of synapses:-
Electrical Vs. Chemical
A. Electrical Synapses
Occur at gap junctions.
Channels (connexon) connect the cytoplasm of presynaptic
& postsynaptic cells.
Current generated by V-G channels at presynaptic neuron
flows directly into the postsynaptic neuron.
Extremely rapid (<0.1 msec).
Permit the bidirectional passage of ions.

B. Chemical Synapses
There is no connectivity b/n the cytoplasm of presynaptic &
postsynaptic neuron.
They are separated by synaptic cleft.
Charges and ions do not move directly b/n cells.
Communication is achieved by chemical means
(neurotransmitters).
Operate in one direction only (presynaptic neuron →
postsynaptic neuron).
Synaptic delay: 0.5ms

Sequence of events at chemical synapses:
Action potential in presynaptic cell
↓
Depolarization of plasma membrane of the presynaptic axon terminal.
↓
Entry of Ca2+
into presynaptic terminal.
↓
Release of the transmitter by the presynaptic terminal.
↓
Chemical combination of the transmitter with specific receptors in
the plasma membrane of the postsynaptic cell.
↓
Transient change in the conductance of the postsynaptic plasma membrane
to specific ions.
↓
Transient change in the Em of the postsynaptic cell.

• There are 2 types of chemical synapses
1. Excitatory chemical synapses- Excitatory postsynaptic potential
(EPSP)
• Transient depolarization
• MP moves closer to threshold
• Na+
influx causes depolarization
2. Inhibitory chemical synapses- Inhibitory postsynaptic potential
(IPSP)
• Transient hyperpolarization
• MP moves farther away from its threshold
• Produced by Cl-
influx & accelerated K+
efflux

Fates of the Neurotransmitter
NT must be inactivated or removed from the postsynaptic cleft
after its has produced the appropriate response in the
postsynaptic neuron
Mechanisms: 3
1. Diffusion: NT diffuses away from synapse into the nearby
ECF
2. Reuptake: into the synaptic knob of presynaptic neuron
3. Internalization of the receptor
4. Enzyme degradation
e.g. Acetylcholine (ACh) acetylcholinesterase(AChE) acetate +
choline

Quiz
1. What is axon hillock?
2. What is the node of ranvier?
3. What are the types of synapses?
4. What are the parts of synapse?
5. List atleast 3 characteristics of action potential.

50
Muscle
• Comprises largest group of tissues.
• Accounts half of body’s weight.
• 3 Types
1. Skeletal muscle: makes up 40% of body
weight in men and 32% in women
2. Smooth muscle making up another 10%
3. Cardiac muscle of the total body wt.

Skeletal muscles
 Located attached to bones & moves skeleton
 They are elongated, cylindrical and peripheral
multinucleated cells
 They are striated muscle (have visible striations)
 They are voluntary muscle, controlled by somatic nerve
system

Cardiac muscle
 Muscle of the heart
 Are striated muscle
 Are branched cells.
 Have single centrally located nucleus
 Involuntary, controlled by autonomic nerve system
(involuntary nerve)
 Have the property of autorhythmicity and syncytium

Smooth muscles
 Located in the wall of hallow organs (GIT, blood vessels,
uterus, urinary bladder, Iris)
 Are spindle-shaped cells
 Have single centrally located nucleus
 They have non-striated appearance
 Involuntary muscle, controlled by autonomic nerve system
 Have the property of autorhythmicity and syncytium

54
Characteristics and functions of muscle tissue
• Muscle tissue has 4 principal characteristics:
1. Excitability – property of receiving and responding to
stimuli.
2. Contractility – ability to shorten and thicken (contract).
3. Extensibility – ability to be stretched (extended).
4. Elasticity - ability to return to original shape after
contraction or extension.

55
Functions of muscle
• Movement (both voluntary and involuntary)
• Maintenance of posture
• Heat production
• Support soft tissues
• Guard entrances & exits
• Store nutrient reserves (e.g. glycogen & protein)
• Moves blood through the circulatory system

56
Structure of skeletal muscle
• Attached to bone by tendons composed of connective tissue.
• This connective tissue also encircle entire muscle & is called
epimysium.
• Skeletal muscles consist of numerous subunits or bundles called
fascicles .
• Fascicles are also surrounded by connective tissue called
perimysium
• Each fascicle is composed of numerous muscle fibers (muscle
cells).

59
• Muscle cells, ensheathed by endomysium, consist of many
fibrils (or myofibrils).
• Myofibrils: specialized contractile elements
80% of the volume of the muscle fiber
Made up of long protein molecules called myofilaments.
• There are two types of myofilaments in myofibrils:
Thick myofilaments
Thin myofilaments

60
Cell membrane of muscle
Sarcolemma
• Maintains a membrane potential (like neurons memb.)
• Impulses in muscle cells → bring about contraction.
• Transverse tubules (or T-tubules ):
Invagination of surface of sarcolemma.
One end is open to extracellular space.
Function : conduct impulses from surface of sarcolemma to
the sarcoplasmic reticulum.

61
Sarcoplasmic reticulum (SR)
• Internal tubular structure that surrounds each myofibrils
• All types of muscle require calcium for contraction
• Ca2+
(in skeletal muscle) store in terminal cisternae (lateral sacs)
• Membrane of SR is well-equipped to handle calcium.
1. It contains Ca2+
-ATPase (Ca2+
pump)
 Transports Ca2+
from ICF to SR, keeping intracellular Ca2+
low.
• In a relaxed muscle - [Ca2+
] in SR ↑
- [Ca2+
] in the sarcoplasm ↓

62
2. It has special openings, or "gates", for calcium.
• Ryanodine receptor channels → Ca2+
release channels
• In a relaxed muscle, these gates are closed so, the calcium remains
in the SR.
• However, if an impulse travels down , calcium "gates" open .
Calcium diffuses rapidly out of SR to sarcoplasm where the
myofibrils & myofilaments are located.
 This is a key step in muscle contraction.

64
Myofibrils
• Myofibrils are composed of 2 types of myofilaments
Thick myofilaments
 Thin myofilaments
• They are arranged longitudinally in sarcomeres.
• Sarcomeres are the functional units of skeletal muscle.
• In each sarcomere,
Thin myofilaments extend in from each end.
Thick myofilaments are found in the middle of the sarcomere
and do not extend to the ends.

65
• When skeletal muscle is viewed with a microscope:
The ends of a sarcomere (where only thin myofilaments are
found) appear lighter
The central section is dark (b/c of the presence of the thick
myofilaments).
• Thus, a myofibril has alternating light and dark areas & this is
why skeletal muscle is called striated muscle

67
Components of sarcomere
A band:
• The darker areas
• Thick and thin filaments overlap
• Thick filaments lie only within A band and extend its entire
width
H zone:
• Lighter area within the middle of the A band
• Thin filaments do not reach
• Only the central portions of the thick filaments are found

68
M line:
• Extends vertically down the middle of the A band within the
center of the H zone.
I band:
• The lighter areas
• Thin filaments that do not project into the A band
Z line:
• A thin dark line near the center of each I-band
• Connects the thin filaments of two adjoining sarcomeres
• The area between two Z lines is called a sarcomere

70
Thin and Thick filament
Thick filament
• Composed of a protein called myosin
• Myosin has:
A tail (forms the core of the thick myofilament)
A head possess actin binding site + ATPase activity (requires
the physical contact with actin)
• These myosin heads are also commonly referred to as cross-
bridges.

72
Thin Filament
• Thin filament contains :
1. Actin:
The primary structural proteins of the thin filament
F & G types
• G actin has a binding site for myosin
2. Tropomyosin
A rod-shaped molecule stretched along each strand of thin
filament.
It blocks the binding sites of myosin on actin.

73
3. Troponin:
• Small globular units located at intervals along the tropomyosin
molecules.
Tn-T = attaches the troponin complex to tropomyosin.
Tn-I = inhibits the interaction of actin and myosin.
Tn-C = the Ca2+
- binding protein that, when bound to Ca2+
,
permits the interaction of actin and myosin.
• Calcium binding to troponin regulates skeletal muscle contraction.
• NB: Troponin & tropomyosin are regulatory proteins

84
Molecular Basis of Skeletal Muscle Contraction
Sliding filament mechanism:
• Thin filaments on each side of a sarcomere slide inward over the
stationary thick filaments toward the A band’s center during
contraction
Thin filaments pull Z lines to which they are attached closer
together
Sarcomere shortens
If all sarcomeres shorten simultaneously, entire fiber shortens
This is the sliding filament mechanism of muscle contraction

85
(a) Relaxed
1. No excitation
2. No cross-bridge binding because cross-
bridge binding site on actin is physically
covered by troponin-tropomyosin
3. Muscle fiber is relaxed.
complex
.

86
(b) Excited
1. Muscle fiber is excited and Ca2+
is
released from SR
2. Released Ca2+
binds with troponin, pulling cross-
troponin-tropomyosin complex aside to expose
3. Cross-bridge binding occurs
4. Binding of actin and myosin cross bridge triggers power
stroke that pulls thin filament inward during contraction.
bridge binding site

87
The power strokes of all cross bridges extending from a thick
filament are directed toward the center of the thick filament.

88
Changes in banding pattern during shortening

89
Innervations of the skeletal muscle
• A skeletal muscle is supplied by a group of motor nerve fibers.
• After entering the muscle, each motor nerve fiber divides in to
several branches.
• Motor unit:- one motor neuron plus all the muscle fibers it
innervates.
• The junction between the nerve fiber and the muscle fiber is
called the neuromuscular junction or motor end plate.

90
Fig. Innervations of the skeletal muscle

 The smaller the motor unit, the finer and more delicate the
movements.
 Extraocular muscles typically have small motor units while
the large postural muscles have large motor units.

92
Excitation-Contraction Coupling
• Refers to the series of events linking muscle excitation to
muscle contraction
Dependent on
(1) neural input from motor neuron
(2) calcium release from the SR
• Calcium is the link between excitation and contraction.

93
Steps
1. Ach is released from axon terminal of the somatic motor
neuron via exocytosis.
2. Ach cross the synaptic cleft thr’ diffusion and bind to its
receptor (nicotinic receptor) on the motor end plate.
3. This binding elicits an end plate potential which triggers an
AP in the muscle cell.
4. AP propagates along sarcolemma
5. Then, it travels down the T tubules

94
6. DHP receptors (V-G calcium channel) of T tubules open Ca2+
release channels (ryanodine receptors) in lateral sacs of SR.
7. Calcium increases in sarcoplasm
8. Calcium binds to troponinC shifting troponin-tropomyosin
complex from myosin binding site on the actin .
9. Binding of myosin head to actin (Cross bridge cycling occurs
(contraction)

95
Fig . propagation of AP through T-tube

98
Termination of Contraction
• Neural excitation/Ach release should
cease.
• Calcium must leave troponin
• To remove calcium from sarcoplasm
Ca2+
-ATPase transports calcium from
sarcoplasm into SR

ATP is used by muscle during:
• Cross bridge cycling (contraction)
• Active transport of calcium into SR (during relaxation)
• Na+
/K+
Pump
 Maintain ion gradients and membrane potential

100
Twitch Contraction
• Is a single muscle contraction in response to a single stimulus
and lasts from 20msec to 200msec.
Parts of a Twitch Contraction
 Latent Period--2msec
Time during which impulse is travelling along the
sarcolemma & down T-tubule to the SR and Ca+2
is being
released from SR.

 Contraction Period
10 to 100 msec (average about 50msec)
Filaments slide past each other
 Relaxation Period
10 to 100 msec (average about 50msec)
Active transport of Ca+2
into SR

104
Refractory Period
• Muscle cannot respond and has lost its excitability
• 5 msec for skeletal & 300 msec for cardiac muscle
• Skeletal muscles have short refractory period (ends in the
latent period).
• Because of this skeletal muscles are prone to fatigue (a
decrease in or absence of response to stimulus)
• Can we tetanize skeletal muscle?

105
Summation of Contractions
• Repeated stimulation before relaxation.
• Produces additional activation of contractile elements.
• Similar to temporal summation of EPSPs at postsynaptic neuron
• With rapidly repeated stimulation, the individual responses fuse
(add together) into one continuous contraction.
• Such a response is called a tetanus (tetanic contraction).

107
Types of Muscle Contraction
• There are two primary types of muscle contraction
A. Isometric contraction
• Occurs when muscle develops tension and exerts force on an
object, but does not shorten.
• Examples:
• Supporting an object in a fixed position, such as carrying a
book
• Attempting to move an object that is too heavy to shift or
reposition

109
B. Isotonic contraction
• Muscle tension remains constant as the muscle changes length
• Are used for body movements and for moving external objects.
A. Concentric isotonic contraction:
B. Eccentric isotonic contraction:
• Examples:
• Lifting an object, with muscle shortened in the process
 Because weight of the object does not change as it is lifted,
muscle tension remains constant

111
Clinical Correlates
1. Rigor Mortis
• Occurs after death.
• Contracture, i.e., contraction produced without AP and not
followed by relaxation.
• The rigidity is due to depletion of ATP
• Disappears when muscle fibers are autolysed
• Starts to disappear 14hrs after death and completed in 24hrs.
• Extent of rigor mortis is used medically to determine time of death.

2. Myasthenia gravis
• It is an autoimmune disease
• Causes paralysis
• The cause is destruction of Ach receptors by antibodies.
3. Botulinium toxin:
• Obtained from the bacteria, Clostridium botulinium
• It prevents the release of Ach → transmission of impulse is
failed → paralysis of the skeletal muscles → death

113
4. Muscular Atrophy and Hypertrophy
• Muscular atrophy refers to a state of wasting away, or
decrease in size, of muscle tissue.
There are 2 types of muscle atrophy: disuse atrophy &
denervation atrophy.
• Muscular hypertrophy refers to an increase in the diameter of
myofibers, resulting in muscular enlargement or overgrowth.
Very forceful muscular activity or repetitive activity at
moderate levels can cause hypertrophy.

117
5. Tetany and fatigue
• Tetany is a smooth sustained contraction of skeletal muscle with
partial relaxation or without relaxation.
• It results from frequent stimulation of the muscle.
• Skeletal muscle can develop tetany because of its short
refractory period.

05. Exitable tissues.pptx it is important

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