| Abstract: | The side chain of arginine, n-propylguanidinium (nPG), reversibly decreases peak sodium conductance and increases the speed of sodium current decay, when perfused internally. Effects are voltage dependent and are more pronounced at high depolarizations. Results are also dependent on the sodium concentration gradient. Both the decline in peak conductance and the speeding of inactivation are greater if the sodium concentration gradient is reversed from the normal. The decrease in peak sodium current is too large to be due solely to the faster decay kinetics. The difference is not due to a change in slow inactivation of the channel. Sodium current inactivation has also been studied with a double pulse procedure. Results show that at - 70 mV, nPG leaves sodium channels rapidly (less than 500 microseconds) in normal sodium gradient, but more slowly (greater than 1 ms) in reversed sodium gradient. Several structural analogs of nPG have been tested. Shortening the alkyl chain weakens effects significantly. Arginine itself, which contains extra charged groups, is also less effective. n-Propylammonium is active but with an apparent affinity only one-fifth that of arginine. We conclude that nPG acts within the sodium channel, and has at least two modes of action. |
