Effects of a sulfhydryl reagent, [formula omitted], on electrical and mechanical activities of isolated atria

Abstract

Rabbit sino-atrial node-right atrium preparations, sympathetic nerve-atria preparations and left atrium preparations were used. N- ethylmaleimide (NEM) in concentrations higher than 10 −5 M produced a dose-dependent decrease in atrial rate. At 10 −3 M activities the S-A node and right atrium were abolished. The activities were not restored by cysteine and ATP. Transmembrane potentials of S-A nodal pacemaker fibers were affected by 10 −3 M NEM. The major changes consisted of a decrease in the slope of diastolic depolarization and an acceleration of repolarization velocity. A tendency for the maximal diastolic potential and the overshoot to decrease were observed. Pacemaker shift frequently occurred. S-A nodal activities were more resistant to NEM than those of the right atrium. Left atrial preparations were driven electrically at different rates. The developed tension-driving rate relationship was not influenced by 10 −5 M NEM but was measurably depressed by 10 −4 M. The depression of the tension developed at high driving rates (60 to 240 beats/min) was more marked than that at low rates (6 to 30 beats/min). The negative chronotropic response to transmural electrical stimulation applied at the S-A node was slightly reduced in some preparations exposed to 10 −7 to 10 −5 M NEM, but was blocked by 10 −4 M. At the same concentration, slowing of atrial rate produced by acetylcholine was also blocked. The positive chronotropic effect of sympathetic nerve stimulation and of noradrenaline was reduced by 10 −4 M NEM. Since the effects of NEM were prevented by preincubation with isomolar concentrations of cysteine, the changes observed were considered to result from an inhibition of the SH groups. Thus, it was concluded that SH groups are involved in the process of contraction and the bioelectrical activity of pacemaker membrane linking automaticity and chronotropic actions of acetylcholine.