Ion Channels from Mammalian Brain and Heart, Incorporated into Planar Lipid Bilayers. Regulation by Membrane Potential, Calcium, and Neurotoxins

摘要

Voltage-dependent sodium channels and calcium channels have been studied at the single channel level in artificial planar phospolipid bilayer membranes. Sodium channels are responsible for impulse generation in nerve and muscle and constitute the only site of actions of the neurotoxins saxitoxin (STX) and tetrodotoxin (TTX). The sodium channels retain normal function in the artificial membrane. Membrane depolarization reduces the potency of STX and TTX. Experiments employing well-defined ion composition on both sides of the channel as well as chemical modification of the STX binding site, revealed previously unknown blocking effects of calcium ions on sodium movement through the channels. Calcium channels control the entry of calcium ions into nerve terminals and thus modulate release of neurotransmitters. Calcium channels in planar bilayers display voltage-dependent opening and closing, selectivity for divalent cations and block by calcium channel inhibitors. The probability of channel closing is inversely proportional to the rate of permeant ion movement through the channel, suggesting that only unoccupied channels can close.