1. The Neuron

• Types of neurons: (Eckert, Fig. 5-1) (Eckert, Fig. 5-2)
• Synaptic connections show a graded electrical response whereas transmission along nerve axons is all-or-none: (Eckert, Fig. 5-4)

2. The action potential - basics

• A threshold depolarization is needed to elicit an action potential: (Eckert, Fig. 5-16)
• The action potential is a time course of potential change along the axon of a neuron. The action potential begins with the opening of voltage-gated channels that increase the permeability of the membrane to Na⁺. As a result of this change in permeability, Na⁺ can enter the cell. Only a little Na⁺ enters but the potential for diffusion of Na⁺ into the cell is very great. Why? Well, the permeability of the membrane to K⁺ remains at its normal levels for a short time while the permeability of the membrane to Na⁺ rises to and far beyond the value for K⁺ permeability. So, Na⁺ becomes the major ion to which the membrane is permeable and the Nernst equation with Na⁺ is now the proper equation to be used to calculate membrane potential.
• Now let's repeat our calculation for the peak of the action potential when the permeability to Na⁺ is very high and the permeability to Na⁺ and Na⁺ remain at much lower levels: Suppose that Na_out = 100 mM and Na_in = 10 mM. Then V = +62 mV.
• So, the membrane potential rises from something like -62mv. towards +62mv, but decreases back to resting levels, as Na⁺ channels close and become inactivated. (vertebrate myelinated neuron) , (the "domino effect")

3. Experiments on the squid giant axon show how the particular shape of the action potential is related to conductance changes.

• Replacement of Sodium in the external bathing solution causes action potential to disappear! (Eckert, Spotlight Fig. 5-4d)
• Voltage-clamping experiments show allow us to see how much of the total transmembrane electrical current is carried by 1) both Potassium and Sodium and 2) by Potassium alone. (Eckert, Fig. 5-21) These experiments were later extended so that the clamping voltage was controlled to look like a normal action potential. Thus the currents represented those found in a normally produced action potential.
• Conductance changes were calculated knowing how much of the current was carried by each ion, such as I_Na, and the voltage V. Ohms law is V = (1/g_Na)I_Na or I_Na = g_NaV
• At rest (1 - figure below), the sodium conductance is very low relative to either potassium or chloride conductances. (Typically, sodium conductance is 1/100 of potassium conductance.)
• After initiation of the action potential, the sodium conductance rises very rapidly, quickly becoming much larger than either the potassium or chloride conductance. Remember that membrane potential is determined by the relative conductances or permeabilities of the membrane to various ions, not the absolute values of conductances or permeabilities. So, when the sodium conductance becomes very large relative to the other conductances, the membrane potential approaches the sodium Nernst potential, V_Na (2).
• The membrane never quite reaches the actual sodium Nernst potential because of electrical capacitance - The sodium conductance is falling rapidly after its peak and the membrane potential never quite "catches up" to the conductance changes - There is a time lag between the two.

• During the initial phase of the action potential, potassium conductance, g_K has been rising. Notice that after the peak of sodium conductance, the ratio of g_K/g_Na is increasing very rapidly as the result of the simultaneous increase of g_K and decrease of g_Na (3). So, the increase in g_K causes the action potential to decrease back towards the resting potential more rapidly than it would be expected to if g_K did not change. Experimentally, we find that if the membrane channels for potassium are blocked by a chemical inhibitor, the action potential is prolonged!
• Finally, notice that g_K remains high for awhile. Since the potassium and chloride Nernst potentials are not quite the same - the potassium Nernst potential is somewhat lower than the resting potential - the effect of high g_K, with g_Cl remaining constant, is to produce an "afterpotential" (4). The membrane potential is near the Nernst potential for the ion to which the membrane is primarily permeable - potassium! This particular type of afterpotential is called a positive afterpotential because the first recordings of membrane potential were reversed as compared with modern recordings - They didn't have intracellular electrodes and had to measure potentials with two electrodes on the outside of the cell - one near where the potential was changing and one some distance away where the potential was constant!

4. Studying the channel proteins:

• Poisons and and a drug: Tetrodotoxin (TTX) from the Japanese puffer fish blocks sodium channels. Puffer fish or fugu can be eaten as sushi, if one wishes to take the risk! Batrachotoxin, from poison arrow frogs of South America, blocks sodium channels with an effectiveness that far exceeds that of TTX. Verapamil is a medication used to treat high blood pressure. It partially blocks the action of voltage-gated Calcium channels!
• Potassium channels consist of multiple protein helicies that span the membrane. Looking down at the surface of a cell membrane we would see the helicies surrounding a pore, through which the potassium ion would move: (Eckert, Fig. 5-25c).
• The voltage-gated sodium channel looks very similar: (Eckert, Fig. 5-26a).

All text and images, not attributed to others, including course examinations and sample questions, are Copyright, 2008, Thomas J. Herbert and may not be used for any commercial purpose without the express written permission of Thomas J. Herbert.