Exam 2- Block 2 Lecture 4 (graded potentials and action potentials)

KNOW Distribution of channels and pumps in the segments of the neuron Differences and similarities between graded potentials and action potentials Phases of action potential generation, changes in permeability, and the refractory periods The cycle of the Voltage Gate sodium Chanel Propagation of the Action Potential

Chemically gated channel vs voltage-gated channel

How are they gated?

Where are they located?

• The major difference between a chemically gated ion channel and a voltage-gated ion channel is how they are gated or opened. Chemically gated channels are opened following the binding of a chemical (most commonly a neurotransmitter).

  • This binding causes a conformational change in the receptor opening the channel through which

    ions can pass.

  • These types of ion channels are located in the dendrites and the neuronal cell body where axon terminals from other neurons are present.

• Voltage-gated channels are opened following a change in membrane potential. The change in membrane potential causes the protein to undergo a conformational change that opens the channel allowing ions to pass.

  • These types of channels are located in the axon hillock, throughout the axon, and in the axon terminals.

Which functional segments of a neuron contain chemically gated channels?

Which functional segments contain voltage-gated channels?

• The receptive segments of a neuron (dendrites and cell body) contain chemically gated channels. The axon hillock (trigger zone), conductive region (axon), and terminal contain voltage-gated channels.

• The selectivity of voltage-gated channels will change in the different segments: voltage-gated sodium and potassium channels are found along the axon and terminal, while voltage-gated calcium channels are located only in the terminal.

Describe the 3 states of the voltage-gated sodium channel. What factors mediate the transitions between each state?

How does the anatomy and physiology of the voltage-gated sodium channel contribute to the positive feedback loop seen in the rising phase of the action potential?

The voltage-gated sodium channel will always exist in one of three states: closed (resting) state, open (activation) state, inactive (inactivation) state.

• Resting

  • The movement through these states is unidirectional, such that the channel will

    only move from open to inactive to closed and back to open. The channel cannot go directly from inactive back to

    open. The reason the voltage-gated sodium channel can exist in these three states is the presence of two (2) separate

    channel gates, an activation gate, and an inactivation gate.

• Activation

  • he activation gate is the gate the responds to the change in voltage across the membrane, and thus is the gate that will open first. Opening this gate moves the channel from the closed state to the open state.

• Inactive

  • Once the activation gate opens, there is a fixed period of time before the inactivation swings into the channel and blocks the flow of ions. As the cell begins to repolarize, the activation gate closes again and the inactivation gate is removed. Following this transition, the channel is back in the closed state and is ready to complete another cycle.

What is the significance of the threshold membrane potential in the initial segment of a neuron?

• The threshold membrane potential is the level of membrane depolarization where that depolarization becomes self-generating and the sodium channel positive feedback loop drives the exponential change in membrane potential.

• The existence of the threshold is dictated by the high concentration of voltage-gated sodium channels at the axon hillock and the strong electrochemical gradient of sodium. This threshold potential is also responsible for the ‘all or none’ nature of the action potential. If a stimulus reaches threshold potential, an action potential is generated, but if the stimulus is sub-threshold, then no action potential is generated.

Know how to draw an action potential and where to label the following: resting membrane potential, threshold, depolarizing phase, repolarizing phase, absolute refractory period, and relative refractory period.

During what phase is Na + permeability the greatest? During what phase is K+ permeability the greatest?

(Slides 21 and 22 in the lecture PowerPoint have a good summary drawing of the action potential and associated permeability changes.

Compare and contrast graded potentials and action potentials.

• Where are they generated?

- Graded potentials: Dendrites and cell body (where you have synapses)

- Action potentials: axon hillock (where you have a high concentration of voltage-gated sodium channels)

• What channels do you need?

- Graded potentials: chemically gated ion channels (neurotransmitter binding)

- Action potentials: voltage-gated ion channels (sodium first, and then potassium)

• The direction of voltage change?

- Graded potentials: positive (depolarization) or negative (hyperpolarization)

- Action potentials: positive (depolarization) and then negative (repolarization)

• Amount & degree of voltage change?

- Graded potentials: relatively small amount and dependent on magnitude of the stimulus (more neurotransmitter released, more chemically gated ion channels opened, larger graded potential)

- Action potentials: relatively large change (complete change in polarity from -70mV to +30mV), but degree does not change (all action potentials will have the same shape and magnitude)

• Duration of event?

- Graded potential: short (will decay with distance)

- Action potential: long, travel the complete distance of the axon through propagation

• Change in intensity?

- Graded potentials: amplitude of events will decrease over distance (no means of regeneration)

- Action potentials: The amplitude of events will always be the same

How does depolarization and repolarization occur in the conductive segment of a neuron?

• Once you have generated an action potential it needs to be propagated down the axon.

  • This is accomplished by the flow of current down the axon.

• Once the action potential is initiated and the depolarization phase begins, that local current that is generated in the axon hillock is attracted toward the more negative regions of the axon (i.e. down the axon toward the axon terminals). This causes voltage-gated sodium channels in this more distal part of the axon to open allowing that region of membrane to become depolarized. In this manner, a wave of depolarization can travel down the axon, with each more distal region of the axon opening voltage-gated sodium channels in response to the depolarization of the more proximal region.

• All of these axon segments also contain voltage-gated potassium channels that will facilitate the repolarization phase. Just as repolarization followed depolarization when the action potential was generated at the axon hillock, this cycle of changes in membrane potential will be repeated all the way down the axon. You can think of action potential propagation as a wave of depolarization followed by a wave of repolarization all the way to the axon terminals.

How does conduction of an action potential in an unmyelinated axon and myelinated axon differ?

• In an unmyelinated axon the conduction of an action potential is relatively slow because the process of depolarization and repolarization must be constantly repeated all the way down the axon.

  • If you did not have a continuous wave of depolarization and repolarization down the axon, the signal would be lost as the current generated by an action potential decayed (similar to a graded potential).

  • In a myelinated axon, the process of action potential propagation can take breaks under the myelin sheath. When myelin is present there is an increase in membrane resistance from the myelin that inhibits current from leaving the axon, and the only direction current can flow is down the axon. Due to this increased membrane resistance, the action potential can move passively under the myelin sheath with very little change in amplitude. When the leading wave of depolarization from the action potential emerges at the node of Ranvier, the voltage-gated sodium channels that are concentrated there will open, and initiate an action potential at that site, creating a large current that will flow inside the axon to the next node.

When a neuron exits its absolute refractory period, its voltage gated sodium channels are changing from:

inactivated state to resting state

In a myelinated axon, the greatest concentration of voltage-gated ion channels is in the:

Nodes of Ranvier

During the relative refractory period of the action potential, what can happen?

It is possible to generate an action potential with a large stimulus

The speed of propagation of an action potential in an axon is increased by what?

Creating myelin sheath around segments of the axon

Why is the threshold value of the membrane potential important to action potential generation?

It is the point where depolarization becomes self-generating