Voltage-dependent changes in the permeability of nerve membranes to calcium and other divalent cations

Transmitter release from depolarized nerve terminals seems to be preceded by a rise in the intracellular concentration of ionized calcium. In squid giant axons, depolarization promotes calcium entry by two routes: one that is blocked by tetrodotoxin and one that is insensitive to tetrodotoxin. The TTX-sensitive route seems to be the sodium channel of the action potential; but the TTX-insensitive route seems to be quite distinct from the sodium and potassium channels of the action potential. It is blocked by Mg-2+, Mn-2+ and Co-2+ ions and by the organic calcium antagonist D-600 and has many features in common with the mechanism that couples excitation to secretion.