Types of Ion Channels Leak channels some are always open (open and close randomly) e.g., K+ leak channels cause nerve and muscle cell membranes to be more permeable to K+ than to Na+. Gated channels (Even though the behavior of an individual channel may appear to be random, the stimulus significantly changes the probability of a population of channels being open or closed.) voltage-gated channels open/close due to changes in membrane potential e.g., voltage-gated channels for Na+, K+, and Ca++ ligand-gated channels (“chemically-gated”) open/close due to the binding (ligation) of a chemical signal (ligand) e.g., The nicotinic cholinergic receptor opens when acetylcholine (ACh) binds to it. mechanically-gated channels open/close due to a mechanical stimulus e.g., sensory receptors that respond to pressure or stretch

Examples of Gated Channels e.g., voltage-gated K+ channel e.g., nicotinic cholinergic receptor Fig. 11-21 Alberts et al., Molecular Biology of the Cell

Voltage-gated Na+ Channel Fig. 14-2 Katzung, Pharmacology Voltage-gated Na+ Channel three states: resting, activated, and inactivated resting activation gate (m) closed, inactivation (h) gate open activated activation gate open, inactivation gate open stimulus for opening: depolarization time to start opening: ~ 0.1 msec inactivated activation gate open, inactivation gate closed stimulus for closing: depolarization time to start closing: ~ 0.2 msec recovery: When the membrane returns to the resting membrane potential, the Na+ channels return to the resting state.

Voltage-gated K+ Channel two states: closed and open Fig. 12.14 plus Fig.11-21, Alberts open stimulus for opening: depolarization time to start opening: ~ 0.2 msec closed during resting state inactivated In some neurons (e.g., rapidly firing neurons) the K+ channel also has an inactivated state. Alberts et al., Molecular Biology of the Cell

Voltage-gated Na+ and K+ Channels one stimulus, three responses /activated Panel 11-3, Alberts et al., Molecular Biology of the Cell

changes in the channels Fig. 12.14 - altered with channel cartoons from Katzung and Alberts Action Potentials changes in the channels Stimulus t = 0 0.1 ms [positive feedback] 0.2-0.3 ms

Reminder: Since depolarization, repolarization and after-hyperpolarization are due to the diffusion of Na+ and K+ through voltage-gated Na+ and K+ channels, the membrane potential cannot go higher than ENa (e.g., +60 mV) or lower than EK (e.g., –90 mV). Moffett, Moffett and Schauf, Human Physiology

Role of ATP ATP is not directly needed for the production of an action potential. Very few ions cross the membrane. So few that depletion of the sodium and potassium gradients takes hundreds of thousands of action potentials. Over the long term, however, ATP energy is required to empower the Na+ pump to restore the transmembrane sodium and potassium gradients. “battery charger” function of the sodium pump

Refractory Periods Moffett, Moffett and Schauf, Human Physiology Fig. 12.15 Absolute refractory period: No stimulus can cause an action potential. Na+ channels become inactivated and cannot open. Relative refractory period: A greater than normal stimulus is required in order to trigger an action potential. The distance to threshold is greater: 1) the threshold is higher and 2) the membrane is hyperpolarized (more negative).

Local Anesthetics Local anesthetics of the “-caine” family (e.g., novocaine, benzocaine, lidocaine) block the Na+ channel at its intracellular end. Therefore, their effect is to put the nerve cell membrane into an absolute refractory period. anesthetic Fig. 14.2 Katzung, Pharmacology

Propagation of an Action Potential It is possible for an electrical signal to travel along an axon or a muscle cell in either direction. Nonetheless, in neurons the signal usually travels in only one direction. Direction of movement is determined by what area is excited first.

Propagation of an Action Potential cell body and dendrites: “receiving end” axon terminals: “sending end” One end of the cell is specialized to receive signals. Action potentials start at the part of the axon closest to the receiving end. “Active” depolarization in one place causes depolarization-to-threshold “downstream.” “Upstream” is refractory. The “distal” end of the cell is specialized for sending signals to the next cell. A B C Fig. 12.16