Role of the inward K rectifier in the repetitive activity at the depolarized level in single ventricular myocytes

Abstract

The role of the inward K(+) rectifier in the repetitive activity at depolarized levels was studied in guinea pig single ventricular myocytes by voltage- and current-clamp methods. In action potentials arrested at the plateau by a depolarizing current, small superimposed hyperpolarizing currents caused much larger voltage displacements than at the resting potential and sometimes induced a regenerative repolarization. Around -20 mV, sub- and suprathreshold repetitive inward currents were found. In the same voltage range, small hyperpolarizing currents reversed their polarity. During depolarizing voltage-clamp ramps, around -20 mV there was a sudden decrease in the outward current (I(ns): current underlying the negative slope in the inward K(+) rectifier steady state I-V relation). During repolarizing ramps, the reincrease in outward current was smaller and slower. During depolarizing and repolarizing current ramps, sudden voltage displacements showed a similar asymmetry. Repetitive I(ns) could continue as long as the potential was kept at the level at which they appeared. Depolarizing voltage-clamp steps also caused repetitive I(ns) and depolarizing current steps induced repetitive slow responses. Cadmium and verapamil reduced I(ns) amplitude during the depolarizing ramp. BRL 34915 (cromakalim), an opener of the ATP-sensitive K(+) channel, eliminated the negative slope and I(ns), whereas barium increased I(ns) frequency (an effect abolished by adding BRL). Depolarization-induced slow responses persisted in an NaCl- Ca-free solution. Thus, the mechanism of repetitive activity at the depolarized level appears to be related to the presence of the negative slope in the inward K(+) rectifier I-V relation. Copyright 1994 S. Karger AG, Basel