Comparison of K + currents in cardiac Purkinje cells isolated from rabbit and dog

Abstract

The repolarization reserve determines the ability of drugs to prolong the cardiac action potential duration. Differences in K + currents between rabbit and dog cardiac Purkinje cells were studied by recording the transient outward K + current ( I to) as well as the delayed rectifier K + currents ( I Ks and I Kr) during repolarization. Purkinje fibers were dissected from dog and rabbit hearts and exposed to enzymatic digestion until isolated cells were obtained. Whole cell voltage clamp methods were used to measure K + currents in both cell types. Action potential (AP) recordings from Purkinje cells displayed a rapid phase 1 repolarization due to a prominent I to with densities of 13.3 ± 2.3 and 9.6 ± 0.6 pA/pF at + 40 mV in dog and rabbit respectively. I Ks tail currents were significantly larger in dog Purkinje cells. I Kr tail current densities were comparable in Purkinje cell from both species. Rabbit ventricular and Purkinje cell AP waveforms were used for action potential clamp experiments in TSA201 cells expressing human ether a go–go related gene (HERG). HERG currents elicited by the ventricular waveform reached its maximum amplitude during phase 3 repolarization. In contrast, Purkinje cell AP waveform elicited markedly smaller HERG currents even though the action potential duration was longer. The observations suggest that the fast phase 1 and negative plateau of the Purkinje cell AP limits the contribution of I Kr to repolarization. These results provide evidence that rabbit Purkinje cells have a smaller repolarization reserve and provide a biophysical explanation for a previously observed higher sensitivity to QT prolonging drugs in rabbit than dog Purkinje fibers.