T-type Ca2+ channels are abnormal in genetically determined cardiomyopathic hamster hearts

Abstract

Although there is substantial evidence of abnormal Ca2+ homeostasis in heart cells of the cardiomyopathic Syrian hamster (Bio 14.6 strain), the mechanism by which these myocytes become Ca2+-overloaded is not known. To elucidate the role of voltage-sensitive Ca2+ channels in the pathogenesis of myopathy, whole-cell Ca2+ currents were measured in myopathic and normal control cardiac myocytes. These studies demonstrate the presence of two voltage-sensitive Ca2+ channel types in ventricular myocytes isolated from 200- to 300-day-old cardiomyopathic and age-matched normal hamsters. The two Ca2+ channel types were identified by their unitary conductance properties and pharmacologic sensitivities. Both L-type and T-type Ca2+ channels were present in cardiomyopathic and normal cells. Current density through L-type Ca2+ channels was the same in cardiomyopathic and normal control myocytes. However, the mean current density of T-type Ca2+ channels in cardiomyopathic cells was significantly higher than in normal cells (myopathic, 12.3±1.8 pA/pF; normal, 5.8±1.1 pA/pF; n=8; P