Action PotentialExcitable tissue – Nerve ,muscle contd…..

Learning objectives• Genesis of Action potential • Properties of action potential and

accommodation• Nerve conduction • Conduction velocity of action potential with

saltatory conduction• Synapse and neuromuscular transmission• Types of synaptic arrangement• EPSP and IPSP

Action potential The sequence of rapid changes in the membrane

potential that spread rapidly along the nerve fiber when a threshold stimulus is applied following its restoration to the resting level is called action potential

Three stages1. Resting stage2. Depolarization stage3. Repolarization stage

Terminology

• The usual resting membrane potential is oriented with the cell interior negative.

• Depolarization: it’s the process of making the membrane potential LESS NEGATIVE

• Depolarization makes the interior of the cell less negative, or it may even cause the cell interior to be positive.

• Hyperpolarization: is the process of making the membrane potential more negative

• Threshold potential : it’s the membrane potential at which occurrence of the AP is inevitable.

• The threshold potential is less negative than the resting membrane potential (an inward current is needed for this to happen)

• At threshold potential, the net inward current becomes larger than the net outward current to sustain the threshold.

• Overshoot: that portion of the AP where the membrane potential is positive (cell interior positive)

• Undershoot: is that portion of the AP, following re-polarization where the membrane potential is more negative than at rest.

Action Potentials• PHASES:

• threshold excitation (depolarisation)• rising phase• falling phase (Repolarisation)•undershoot (hyperpolarisation)

Membrane Conductance

• Definition Membrane conductance refers to the number of channels that are open in a membrane. For example, Na+ conductance is proportional to the number of open channels that will allow the Na+ to pass through the membrane.• General properties If conductance is increasing,

channels are opening, and if conductance is decreasing, channels are closing. The rate at which ions move across a membrane depends on the number of open channels and the net force. When ions flow through channels, the cell’s membrane potential changes. However, under physiologic conditions, too few ions flow to produce a significant effect on the ion’s extracellular concentration or the concentration gradient across the membrane.

VOLTAGE GATED Na AND K CHANNE⁺ ⁺ LS1. Voltage gated Na⁺ channels

↙ ↘Activation gate (outside) Inactivation gate( inside )

Delayed 10,000 of a sec. close at R M P. Conformationalchange increases permeability by 500–5000 times

2. Voltage gated K⁺ channelsOpening corresponds with the closure of Na⁺ gates

3. Other ions : Ca⁺ Ca⁺pump acts along with Na⁺ pump in heart and smooth muscleVoltage gated Ca⁺ channel – slow

VOLTAGE GATED NA AND K CHANNELS

Generation of Action Potential

• Tetrodotoxin (TTX) and lidocaine block these voltage-sensitive Na+ channels and abolish action potentials.

Electrical properties of Smooth Muscle1. RMP (-50mv). It is Unstable leading to spontaneous

excitation. 2. Depolarisation due to the entry of Ca++ mainly and Na+ to

a lesser extent.Repolarisation due to delayed K+ efflux & closure of Ca++

channels.3. Sinusoidal waves (Basal electric rhythm) can be recorded

from the longitudinal muscles of stomach and intestine. This decides the frequency of peristalsis.

Mem

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al (m

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-45

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Action potential

K+ efflux

Ca2+ influx

Threshold of VOC’s

Electrical properties of SM – contd.4. Action potentials

- Spike potentials * appears either on the up going or down going wave of sinusoidal wave

* decides the intensity of peristaltic wave- Pacemaker potentials * are generated in multiple foci that shift from place to place

* responsible for spontaneous excitation- Plateau type

* significance not known

Characteristics of an AP

• Stereotypical size and shape

• Propagation

• All or none response

• Refractory period

Stereotypical size and shape• Stereotypical size and shape: Each normal action

potential for a given cell type looks identical, depolarizes to the same potential, and repolarizes back to the same resting potential.

ACTIONPOTENTIAL

Types & duration of AP 1.Spike potential (Nerve fibre

,skeletal muscle ) – 10 to 50m sec

2.Plateau type (Myocardial cell & smooth muscle cell ) – 250 to 350m sec

3.Pace maker type (Conducting system of heart & smooth muscle fibres ) – 100 to 150m sec

Propagation:

• Propagation: An action potential at one site causes depolarization at adjacent sites, bringing those adjacent sites to threshold. Propagation of action potentials from one site to the next is nondecremental.

Initiation & propagation of AP

All or none response---Either the AP occurs or does not occur.

• All-or-none response: An action potential either occurs or does not occur. If an excitable cell is depolarized to threshold in a normal manner, then the occurrence of an action potential is inevitable.

If the membrane potential has not reached the threshold, no action potential can occur.

Refractory period

• Refractory period: the period during which another normal action potential cannot be elicited in an excitable cell.

• Refractory periods can be absolute or relative.

Refractory period

• Absolute refractory period (functional refractory period)-- The absolute refractory period is that period during which no matter how strong the stimulus, it cannot induce a second action potential

• Relative refractory period--The relative refractory period is that period during which a greater than normal stimulus is required to induce a second action potential.

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Accommodation • When a nerve or muscle cell is depolarized slowly

or is held at a depolarized level, the usual threshold potential may pass without an action potential having been fired called accommodation.• occurs because depolarization closes inactivation

gates on the Na+ channels and if depolarization occurs slowly enough, the Na+ channels close and remain closed.• Example: hyperkalemia which causes sustained

depolarisation of the resting membrane.

Interrupting the Positive Feedback Loop: Voltage-Gated Sodium Channels Inactivate • The rising phase of the action potential ends when the positive feedback loop is interrupted. • Two processes break the loop: 1. the inactivation of the voltage-gated sodium channels. 2. the opening of the voltage-gated potassium channels. • The voltage-gated sodium channels have two gates: 1. A voltage-sensitive gate opens as the cell is depolarized. 2. A second, time-sensitive inactivation gate stops the movement of sodium through the channel after the channel has been open for a certain time. • At the resting membrane potential, the voltage sensitive gate is closed. • As the neuron is depolarized, the voltage-sensitive gate opens. • At a certain time after the channel opens, it inactivates. • At the peak of the action potential, voltage-gated sodium channels begin to inactivate. As they inactivate, the inward flow of sodium decreases, and the positive feedback loop is interrupted.

voltage-sensitive gate

time-sensitive gate

resting

depolarized

inactive

Propagation of action potentials In Neuron

Interrupting the Positive Feedback Loop: Voltage-Gated Potassium Channels Open

• The voltage-gated potassium channels respond slowly to depolarization. They begin to open as the membrane depolarizes, but responds so slowly that they become fully activated only after the action potential reaches its peak.

• potassium moves out of the cell as voltage-gated potassium channels open. As potassium moves out, depolarization ends, and the positive feedback loop is broken.

• Both the inactivation of sodium channels and the opening of potassium channels interrupt the positive feedback loop. This ends the rising phase of the action potential.

Repolarization

•We have seen potassium leaving the cell as voltage-gated potassium channels opened. • With less sodium moving into the cell and more potassium moving out, the membrane potential becomes more negative, moving toward its resting value. • This process is called repolarization.

Repolarization

Hyperpolarization • In many neurons, the slow voltage-gated potassium channels remain open after the cell has repolarized. Potassium continues to move out of the cell, causing the membrane potential to become more negative than the resting membrane potential. • This process is called hyperpolarization. • By the end of the hyperpolarization, all the potassium channels are closed.

Hyperpolarization

Factors affecting: Conduction Velocity of the Action Potential

. Size of the action potential:• Cell diameter:• Myelin: The greater the myelination, the greater the

conduction velocity. • (Demyelination (e.g., multiple sclerosis, Guillain-Barre

syndrome): This would decrease the amplitude of the action potential as it travels from node to node. If the action potential arrives below a certain magnitude, another action potential may not be generated and transmission is blocked.)• Thus, Large myelinated fibers =fast conduction

Comparing nerve conduction in an unmyelinated and a myelinated axon. Myelinated axons conduct impulses upto 50 times faster than the fastest unmyelinated axon.

Synaptic Transmission• Synapse: a site where information is transmitted

from one cell to another. Two types; electrical and chemical synapses

• Electrical synapse – information is transmitted electrically. Gap junctions are low resistance pathways found in cardiac muscle and in some types of smooth muscle and account for the very fast conduction in these tissues. Accounts for synchronised contraction of cardiac ventricles, bladder and uterus.

Chemical synapse

Types of synaptic arrangements• One to one - A single action potential in the

presynaptic cell causes a single action potential in the postsynaptic cell.• One to many – A single action potential in a

presynaptic cell causes a burst of action potentials in many postsynaptic cells.• Many-to-one synapses – the commonest

arrangement; many presynaptic cells converge on a postsynaptic cell, these inputs summate, and the sum of the inputs determines whether the postsynaptic cell will fire an action potential.

SYNAPTIC INPUT-EXCITATORY AND INHIBITORY POSTSYNAPTIC POTENTIALS• Excitatory Postsynaptic Potentials(EPSP) - synaptic

inputs that depolarize the postsynaptic cell, bringing the membrane potential closer to threshold and closer to firing an action potential; produced by opening Na+ and K+ channels. Excitatory neurotransmitters include ACh, norepinephrine, epinephrine , dopamine, glutamate, and serotonin.• Inhibitory Postsynaptic Potentials (IPSP) - synaptic

inputs that hyperpolarize the postsynaptic cell; produced by opening of Cl- channels. Inhibitory neurotransmitters are gamma -aminobutyric acid (GABA) and glycine .

Local Anesthetics.

Among the most important stabilizersare the many substances used clinically as local anesthetics, including procaine and tetracaine.

Most of these act directly on the activation gates of the sodium channels, making it much more difficult for these gates to open, thereby reducing membrane excitability.

For a television game show, 16 contestants volunteer to be stranded on a deserted island in the middle of the South China Sea. They must rely on their own survival instincts and skills. During one of the challenges, one team wins a fishing spear. They catch a puffer fish and cook it over the open flames of their barbecue. None of them are very skilled in cooking, but they enjoy the fish anyway. One of the contestants, a worldwide traveler, comments that it tastes like Fugu. After dinner, they all develop a strange tingling around their lips and tongue. They all become weak, and their frailty progresses to paralysis. They all die. What was the cause of death?

A Tetrodotoxin B Botulism C Bacillus cereus food poisoning D Tetanus E Ciguatoxin

A well-meaning third year medical student accidentally pushes an unknown quantity of KCl IV to a patient. If the concentration of potassium outside a neuron were to increase from 4 mEq/L to 8 mEq/L, what would you expect to happen to the minimal stimulus required for initiation of an action potential?

A The minimal stimulus required for initiation of an action potential would remain the same B The minimal stimulus required for initiation of an action potential would increase

C The minimal stimulus required for initiation of an action potential would decrease D The minimal stimulus required for initiation of an action potential would stay the same, but the amplitude of the peak of the action potential would increase E The minimal stimulus required for initiation of an action potential would stay the same, but the conduction velocity of the action potential down an axon would slow

Q : During the upstroke of the nerve action potential

(A) there is net outward current and the cell interior becomes more negative

(B) there is net outward current and the cell interior becomes less negative

(C) there is net inward current and the cell interior becomes more negative

(D) there is net inward current and the cell interior becomes less negative

At which point on the action potential does the Na+current exceed theK+ current?a. Point Ab. Point Bc. Point Cd. Point De. Point E At which point on the action potential is the membrane closest to theNa+ equilibrium potential?a. Point Ab. Point Bc. Point Cd. Point De. Point E