Chapter 4 The Action Potential

Introduction

Action Potential – Cytosol (cytoplasm) has negative charge relative to extracellular

space

– Its pusatile nature allows for neural coding • frequency • Pattern

– Action potential components to be examined• Spike• Nerve impulse

• Discharge

Properties of the Action Potential– Oscilloscopic movement used to visualize

• Rising phase, overshoot, falling phase, and undershoot

The Generation of an Action Potential

– Caused by depolarization of membrane beyond threshold

– “All-or-none”

For the next series of three slides, please examine them in rapid sequence to create an “animation” of action potential movement in the neuron.

These next two slides show how intensity and frequency of a stimulus can affect generation of action potentials.

Saltatory conduction is the propagation of an action potential along myelinated axons from one Node of Ranvier to the next Node. This process increases the conduction velocity of action potentials without the need to increase the diameter of an axon.

Artificial injection of current (ions) into a neuron (using a microelectrode) can be used to experimentally manipulate a neuron from its interior.

Alan Hodgkin & Andrew Huxley – performed experiments using the patch clamp method that experimentally proved the movement inward of sodium ions and the movement outward of potassium ions during an action potential. This of course, was essential for our current understanding of the biochemistry of this process.

The Voltage Clamp

• used by electrophysiologists to measure the ion currents across the membrane of excitable cells, such as neurons • while holding the membrane voltage at a set level

• cell membranes of excitable cells contain many different kinds of ion channels, some of which are voltage gated

• allows the membrane voltage to be manipulated independently of the ionic currents, allowing the current-voltage relationships of membrane channels to be studied

The voltage clamp technique being used in a segment of giant squid axon.

These are three diagrams of a voltage-gated sodium channel protein.

• in a) we see four regions or domains that will be found in the protein

• in b) we see a close up view of the alpha helix

structures including S4 which is a voltage sensing alpha helix

• also in b) the pore loop is seen which in effect helps

regulate what can pass through the pore

• in c) we see the entire channel in the most common arrangement

In (a) we see the application of a stimulus resulting in the generation of an action potential

In (b) we can see how three different sodium channels may respond slightly differently to the action potential stimulus

In (c) we can see a close up view of the sodium channel protein, this time showing the globular protein (the purple sphere) that serves as a temporary gate to occlude the pore until the membranes themselves close.

Disorders/Diseases Associated with Voltage-Gated Sodium Channel Problems

– Channelopathies - diseases caused by disturbed function of ion channels or channel subunits or the proteins that regulate them

• e.g., Generalized epilepsy with febrile seizures

– Toxins as experimental tools• Toshio Narahashi – ion channel pharmacology• Puffer fish: Tetrodotoxin (TTX)- Clogs Na+ permeable pore• Red Tide: Saxitoxin- Na+ Channel-blocking toxin

Toshio Narahashi – famous pharmacological neuroscientist who uncovered the blocking action of tetrodotoxin.

An example of a startled Pufferfish which produces tetrodotoxin.