The time-dependent and dose-dependent effects of the sulfhydryl blocker N-ethylmaleimide on the tonic tension in bullfrog atrium.

The kinetics of the inhibitory action by N-ethylmaleimide (NEM) on ICa-independent tonic tension in bullfrog atrial muscle was studied under voltage-clamped conditions, using the double sucrose gap method. The higher the concentration of NEM became, the larger was the rate of decrease of the tonic tension. In addition, the tension decreased with time of exposure to NEM. When the rate of the decrease of the tonic tension was plotted as a function of NEM concentration, the curve showed saturation kinetics of the Michaelis-Menten type with respect to NEM concentration, following the characteristics of a carrier-mediated process. Moreover, in the presence of excess Ca or half quantity of Na in Ringer solution, the curve showed sigmoidal kinetics. This probably indicates that the condition of either an excess of Ca or a reduction of Na in Ringer solution is apparently a cooperative effector of the inhibitory action of NEM, suggesting that the carrier protein responsible for the generation of tonic tension may be an allosteric protein. Finally, the relationship between ICa-independent tonic tension and the Na-Ca exchange mechanism which is supposed to be a powerful candidate for generating tension was discussed.