Interactions of monovalent cations with sodium channels in squid axon. II. Modification of pharmacological inactivation gating.

摘要: The time-, frequency-, and voltage-dependent blocking actions of several cationic drug molecules on open Na channels were investigated in voltage-clamped, internally perfused squid giant axons. relative potencies time courses block by the agents (pancuronium [PC], octylguanidinium [C8G], QX-314, 9-aminoacridine [9-AA]) compared different intracellular ionic solutions; specifically, influences internal Cs, tetramethylammonium (TMA), ions examined. TMA+ was found to inhibit steady state all compounds. time-dependent, inactivation-like decay currents pronase-treated axons with either PC, 9-AA, or C8G retarded TMA+. apparent dissociation constants (at zero voltage) for interaction between PC 9-AA their binding sites increased when substituted Cs+ solution. steepness voltage dependence solutions greatly reduced TMA+, resulting estimates fractional electrical distance site 0.56 0.22 respectively. This change may reflect a shift from predominantly presence block. depth, but not rate, frequency-dependent QX-314 is In addition, recovery altered. Elevation produces effects qualitatively similar those seen results are consistent scheme which channel drugs, TMA (and Na) ions, inactivation gate compete access surface. decrease rates other drugs manner analogous inhibition process. Multiple occupancy mutual exclusion play role complex gating behaviors under these conditions.