Effect of "calcium antagonist" D-600 on the postsynaptic membrane.
Using the technique of dialysis of the cell interior (Kostyuk et al., 1978), the effect of "calcium antagonist" D-600 on voltage clamped isolated neurones of mollusc Limnaea stagnalis was studied. Identified giant neurones responding to acetylcholine (ACh) application with changes in conductance for Cl- ions only were used. 1. D-600, 10-100 microM, blocks electroexcitable inward Ca2+-Na+ current in the neurone soma membrane. In the same concentrations, D-600 reduces the amplitude of ACh-induced current and also the time constant of desensitization onset. 2. Voltage jump relaxation experiments show D-600 to decrease the average lifetime, tau, of the Cl- channels opened by ACh, although the effect of d-tubocurarine (d-TC), 10-20 microM, on tau is insignificant. 3. The lifetime of open Cl- channels increases with membrane hyperpolarization; but while the voltage dependence of tau is not altered by d-TC, it is reduced by D-600. 4. The results obtained allow us to suggest that D-600 blocks open Cl- channels. The calculated rate constant of association of D-600 with open channels is of the order of 10(5) M-1 s-1.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005711:Gallopamil / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008974:Mollusca; D012964:Sodium / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects*; D014403:Tubocurarine / Q000494:pharmacology; D014700:Verapamil / Q000031:analogs & derivatives*
D002712:Chlorides; D005711:Gallopamil; D012964:Sodium; D014700:Verapamil; D000109:Acetylcholine; D002118:Calcium; D014403:Tubocurarine