INHIBITION OF TRANSIENT OUTWARD K+ CURRENT BY DHP CA2+ ANTAGONISTS AND AGONISTS IN RABBIT CARDIAC MYOCYTES

The 1,4-dihydropyridine (DHP) Ca2+ antagonists and agonists can inhibit a time- and voltage-dependent, but intracellular Ca2+ -independent transient outward K+ current (I(t)), in myocytes from rabbit atrium. In the presence of 0.3 mM CdCl2, DHPs decreased the peak I(t) slightly and markedly accelerated its apparent rate of inactivation. When the inhibition of I(t) was measured from integrated I(t) records, the 50% inhibitory concentrations (IC50) of nicardipine and BAY K 8644 were 630 nM and 7-mu-M, respectively, and the IC50 of nicardipine for inhibition of the Ca2+ current (I(Ca)) was only approximately fourfold lower (160 nM). The inhibition of I(t) by nicardipine was not affected by changing holding potential from -55 to -100 mV; in contrast, the inhibitory effect on I(Ca) was significantly reduced by this hyperpolarization. We conclude that the DHP Ca2+ antagonist nicardipine blocks I(t) at similar doses to those that block I(Ca) and that nicardipine blocks this K+ current by mechanism different from that for I(Ca) inhibition. This inhibitory effect on I(t) is shared by other DHP compounds; the rank order for potency of I(t) inhibition is nicardipine > benidipine > nisoldipine > BAY K 8644 > nitrendipine > nifedipine.