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ACTION POTENTIAL:
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2. DEFINITIONS:
Stimulus: A stimulus is an external force or event which when applied to an excitable tissue produces a characteristic response. Subthreshold stimulus: A stimulus which is too weak to produce a response is called a Subthreshold stimulus. Threshold stimulus: The minimum strength of stimulus that can produce excitation is called a Threshold stimulus. Suprathreshold stimulus: Stimuli having strengths higher than threshold stimulus are called Suprathreshold stimuli.

3. Channels and their activation
Activation of Channels: Channel opening to allow ion flow is called channel activation. For example, Na channels and K channels of axons are both activated by cell depolarization. The Na channels open very rapidly, but the K channels are slower to open. The result is an initial flow of Na across the membrane, followed later by a flow of K.
Inactivation of Channels: Channel closing and blocking ion flow is called Inactivation. This is similar to doors with an automatic open close mechanism. The door opens when you hit the button, then after a certain period of time, it closes itself, whether you are still standing in the doorway or not. An inactivated channel returns to its normal closed state shortly after the membrane repolarizes.

4. How voltage-gated channels work ?

5. REMEMBER:
Sodium voltage-gated channels: are fast channels & have 2 gates:
- An inner Activation gate(closed in resting state)
- An outer Inactivation gate(open in resting state)
Potassium channels: are slow channels & have only ONE gate.
These channels are different from Sodium & Potassium leak channels.
The Sodium-Potassium PUMP is present separately.

6. Important
When ion channels open, ions may move into or out of the cell.
The direction of ion movement depends on the electrochemical (combined chemical and electrical) gradient of the ion. Potassium ions usually move out of the cell. Sodium, Chloride and Calcium usually flow into the cell. The net flow of ions across the membrane depolarizes or hyperpolarizes the cell, creating an electrical signal.

7. Continue ….
The resting membrane potential of living cells is determined primarily by the K concentration gradient and the cells resting permeability to K, Na, and Cl. A change in either the K concentration gradient or ion permeabilities changes the membrane potential. For example, at rest, the cell membrane of a neuron is only slightly permeable to Na. However, if the membrane suddenly increases its Na permeability, Na enters the cell, moving down its electrochemical gradient. The addition of positive Na to the intracellular fluid depolarizes the cell membrane and creates an electrical signal. The movement of ions across the membrane can also hyperpolarize a cell. If the cell membrane suddenly becomes more permeable to K, positive charge is lost from inside the cell and the cell becomes more negative (hyperpolarizes). A cell may also hyperpolarize if negatively charged ions, such as Cl, enter the cell from the extracellular fluid.

8. Basic concepts
Polarization: Any time the value of the membrane potential is other than 0 mV, in either the positive or negative direction, the membrane is in a state of polarization.
Depolarization: The membrane becomes less polarized; the inside becomes less negative than at resting potential, with the potential moving closer to 0 mV (e.g. a change from – 90 to – 80mv).
Repolarization: The membrane returns to resting potential after having been depolarized.
Hyperpolarization: The membrane becomes more polarized; the inside becomes more negative than at resting potential, with the potential moving even farther from 0 mV (for instance, a change from -90 to -100 mV).

9. Propagation of action potential
When the trace moves upward (becomes less negative), the potential difference between the inside of the cell and the outside (0 mV) decreases, and the cell is said to have depolarized. A return to the resting membrane potential is termed repolarization. If the resting potential moves away from 0 mV, the membrane potential becomes more negative, the potential difference has increased, and the cell has hyperpolarized.

10. Questions
Would a cell with a resting membrane potential of – 70 mV depolarize or hyperpolarize in the following cases? (You must consider both the concentration gradient and the electrical gradient of the ion to determine net ion movement.)
(a) Cell becomes more permeable to Ca2+.
(b) Cell becomes less permeable to K+.
Would the cell membrane depolarize or hyperpolarize if a small amount of Na+ leaked into the cell?
Depolarizes a) Depolarizes.
Depolarizes

11. Action Potential: Definition:
An Action Potential is a self-propagating wave of electro-positivity that passes along the surface of the nerve fibers from the cell body to the axon terminals.
Duration: only 1 msec (same in all neurons).
Also called: A Spike (because of its spike-like appearance).
Action potentials serve as faithful, long-distance signals because they do not diminish in size as they travel from site of initiation throughout the remainder of the cell membrane .
Think about the neuron that causes the muscle cells in your big toe to contract. If you want to wiggle your big toe, commands are sent from your brain down your spinal cord to initiate an action potential at the beginning of this neuron, which is located in the spinal cord. The action potential travels all the way down the neuron’s long axon, which runs through your leg to terminate on your big-toe muscle cells. The signal does not weaken or die off , being instead preserved at full strength from beginning to end.

12. How is the membrane potential, which is usually maintained at a constant resting level, altered to such an extent as to produce an action potential?
During an action potential, marked changes in membrane permeability to Na and K take place, permitting rapid fluxes of these ions down their electrochemical gradients. These ion movements carry the current responsible for the potential changes that occur during an action potential. A threshold or supra threshold stimulus when applied to the neuron causes changes in the voltage that cause opening of the voltage-gated sodium channels. Action potentials take place as a result of the triggered opening and subsequent closing of two specific types of channels: voltage-gated Na channels and voltage-gated K channels.

13. How action potential generated?

14. Phases of an Action Potential
An Action Potential has 3 phases:
Phase 1: Depolarization
Phase 2: Repolarization
Phase 3: Hyperpolarization

15. Phases of action potential

16. State of SODIUM channel gates:
Resting state:
- Inactivation gates: OPEN
- Activation gates: CLOSED
Depolarization:
- Activation gates: OPEN
Peak:
- Inactivation gates: CLOSED
Repolarization:
All are university important MCQs.

17. Voltage-gated Potassium Channels Resting Membrane Potential
Voltage-gated Sodium channels
Depolarization
Voltage-gated Potassium Channels
Repolarization
Hyperpolarization
Resting Membrane Potential
Stimulus

18. Polarized membrane before action potential

19. Opening of Na-channels

20. IONIC BASIS OF AN ACTION POTENTIAL:
DEPOLARIZATION: Sodium (Na) Influx
REPOLARIZATION: Potassium (K) Efflux
HYPERPOLARIZATION: Leakage of excess Potassium (K) ions through the slow closing K channels.
RETURN OF THE AP TO THE RMP FROM HYPERPOLARIZATION: Sodium-Potassium Pump

21. Why does the depolarization not reach the Nernst potential of +66mv for sodium?
There are 2 main reasons. At +35 mv:
Sodium Influx stops because Inactivation gates of Sodium channels close although the activation gates are open & thus no sodium can enter
Potassium Efflux starts because slow Potassium channel gates open and potassium moves out.

22. Timing of opening and closing of different gates

23. Can you differentiate ?

24. DEFINITIONS:
LATENT PERIOD: It is the time period between the application of a stimulus and the start of the response (Action Potential) DEPOLARIZATION: When during the transit changes in the action potential, the Potential difference between the inside of the membrane (-90mv) and outside (0mv) decreases it is called depolarization. ( the tracing will move upwards in the AP diagram) REPOLARIZATION: A return to the resting membrane potential from either direction (i.e. de- or hyper-polarization) is called repolarization. HYPERPOLARIZATION: When during the transit changes in the action potential, the Potential difference between the inside of the membrane (-90mv) and the outside (0mv) increases it is called Hyperpolarization.

25. PROPAGATION OF AN ACTION POTENTIAL:

26. Neuron
It is the basic structural and functional unit of nervous system
Axons vary in length from less than a millimeter in neurons that communicate only with neighboring cells to longer than a meter in neurons that communicate with distant parts of the nervous system or with peripheral organs. For example, the axon of the neuron innervating your big toe must traverse the distance from the origin of its cell body within the spinal cord in the lower region of your back all the way down your leg to your toe.

27. Questions:
Why and how does the action potential spread in the forward direction only?
Why does NOT the action potential spread in the reverse direction?

28. Propagation of action potential

29. Propagation of action potential

30. Propagation of action potential

31. Direction of propagation

32. Unmyelinated Nerve fiber
Once an action potential is initiated at the axon hillock, no further triggering event is necessary to activate the remainder of the nerve fiber. The impulse is automatically conducted throughout the neuron.
For the action potential to spread from the active to the inactive areas, the inactive areas must somehow be depolarized to threshold. This depolarization is accomplished by local current flow between the area already undergoing an action potential and the adjacent inactive area
This depolarizing effect quickly brings the involved inactive area to threshold, at which time the voltage-gated Na channels in this region of the membrane are all thrown open, leading to an action potential in this previously inactive area. Meanwhile, the original active area returns to resting potential as a result of K efflux.
Speed ranges between m/sec in small to large nerev fiber respectively

33. VIVA Question:
Does the action potential become weak (decremental) as it travels down the nerve fiber?
NO, the action potential does NOT become weak as it travels down the nerve fiber. In fact, the AP does NOT travel down the nerve fiber but triggers a new AP in every new part of the membrane. It is like a “wave” at a stadium. Each section of spectators stands up (the rising phase of an action potential), then sits down (the falling phase) in sequence one after another as the wave moves around the stadium. The wave, not individual spectators, travels around the stadium.
Thus, the last action potential at the end of the axon is identical to the original one, no matter how long the axon is. In this way, action potentials can serve as long-distance signals without becoming weak or distorted or decremental.

34. VIVA Question:
Why does NOT the action potential spread in the reverse direction?
If AP were to spread in both directions, which is forward and backward, it would be chaos, with the numerous AP’s bouncing back & forth along the axon until the axon eventually fatigued. This does not happen due to the Refractory period. During and after the generation of an AP, the changing status of the voltage-gated Na and K channels prevents the AP from being generated in these areas again.

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