We examined the effects of amiodarone (5-20 microM) on both whole-cell inward rectifier potassium current (IK1) and single IK1 channel activity in isolated guinea pig ventricular myocytes using patch-clamp techniques. In whole-cell voltage-clamp experiments (n = 8), amiodarone (10-20 microM) caused only a small reduction of outward current at -50 mV (12 +/- 6%, no significant difference, N.S.). However, inward current was significantly reduced at -120 mV (21 +/- 7%; P < .05). When CdCl2 (100 microM) and tetrodotoxin (10 microM) were used to block inward Ca++ and Na+ current, respectively, amiodarone significantly reduced IK1 in both the inward (14 +/- 5% at -120 mV; P < .02) and outward (12 +/- 5% at -50 mV; P < .05; n = 11) directions. However, block required high drug concentrations (10-20 microM) and was slow in onset. In contrast, amiodarone did not affect membrane current when IK1 had been previously blocked by Ba++ (5 mM). In inside-out patch-clamp experiments, amiodarone (5 microM) reduced single IK1 channel open probability by increasing interburst interval (from 0.6 +/- 0.03 to 3.1 +/- 0.9 sec; n = 5; P < .05) with no significant difference in the duration of mean open and closed times or the number of shut events within a burst. The net result was that there was only a small change in both burst duration and single-channel kinetics within a burst. Complete channel block occurred after the increase in interburst interval (n = 6 of six cells).(ABSTRACT TRUNCATED AT 250 WORDS)