EFFECTS OF PIRMENOL ON ACTION-POTENTIALS AND MEMBRANE CURRENTS IN SINGLE ATRIAL MYOCYTES

Electrophysiological effects of pirmenol hydrochloride (pirmenol) were investigated in single atrial myocytes obtained from rabbit and guine a-pig hearts by using a whole-cell clamp technique. Under current clam p conditions, pirmenol (2-30 mu M) prolonged action potential duration in a concentration-dependent manner without affecting resting membran e potential in rabbit atrial myocytes. However, in the presence of 4-a minopyridine (4 mM), pirmenol (10 mu M) failed to prolong the action p otential duration further. Pirmenol also suppressed actetylcholine-ind uced hyperpolarization and action potential duration shortening, resul ting in a significant prolongation of the action potential duration in the presence of acetylcholine. Under voltage clamp conditions, pirmen ol (1-1000 mu M) inhibited transient outward current (I-to) in a conce ntration-dependent manner. The concentration for half-maximal inhibiti on (IC50) of pirmenol on I-to was about 18 mu M. Pirmenol did not show the use and frequency dependent inhibition of I-to. The voltage depen dence of the steady-state inactivation of I-to and the recovery from i nactivation were not significantly affected by pirmenol. Pirmenol acce lerated the inactivation of I-to and blocked I-to as an exponential fu nction of time, consistent with a time-dependent open channel blockade . Pirmenol (30 mu M) did not affect the inwardly rectifying K+ current significantly, but it decreased the voltage-dependent L-type Ca2+ cur rent by about 20%. In guinea-pig atrial myocytes, both acetylcholine a nd adenosine induced a specific K+ current activated by GTP-binding pr oteins. Pirmenol suppressed both the acetylcholine- and adenosine-indu ced K+ current effectively. The IC50 of pirmenol for acetylcholine- an d adenosine-induced current was about 1 and 8 mu M, respectively. The present results suggest that pirmenol prolongs the action potential du ration by primarily inhibiting the transient outward current in atrial myocytes. In addition, since pirmenol inhibits acetylcholine- and ade nosine-induced K+ current, pirmenol may effectively prolong the action potential duration in atrial myocytes under various physiological con ditions as in the whole heart or ischemia. (C) 1998 Elsevier Science B .V.