Regional and frequency-dependent changes in action potentials and transient outward K+ currents in ventricular myocytes from J-2-K cardiomyopathic hamsters.

Abstract

Although lengthening of action potential duration (APD) and decreased transient outward K+ currents (I(to)) have been observed in ventricular myocytes from cardiomyopathic hamsters, epi- and endo-cardial differences in I(to) and their roles in frequency-dependent changes in APD have not been clarified. The patch-clamp technique of whole-cell configuration was used to record membrane potentials and currents in epicardial and endocardial myocytes of the J-2 hamster germline without (control) and with cardiomyopathy (CM). In control, APD in endocardial myocytes was longer than that in epicardial myocytes at 0.1 Hz. APD significantly lengthened with increased frequencies of stimulation from 0.1 to 6.0 Hz in both groups with the longer APD in endocardial myocytes. In CM, APD lengthened in epicardial myocytes exceeding the endocardial APD without a frequency-dependent prolongation. Pretreatment with 4 mM 4-aminopyridine completely abolished the frequency-dependent changes and abolished APD differences between epicardial and endocardial myocytes, and between control and CM hamsters. The transient outward K+ current (I(to)) significantly decreased in epicardial myocytes from CM hamsters compared with that of control (17.5 +/- 1.5 pA/pF in control vs. 9.5 +/- 2.5 pA/pF in CM at +60 mV) with altered recovery from inactivation, without changes in the endocardial I(to). Moreover, the inward rectifier K+ current decreased in epicardial myocytes from CM hamsters and the L-type Ca2+ current reduced in both regions from CM compared to control. Results indicate that differences in APD between epi- and endocardial myocytes in CM hamsters are mainly caused by a decreased current density and altered recovery from inactivation of I(to) in epicardial myocytes.