T-TYPE CA(2-VENTRICULAR MYOCYTES() CURRENT IS EXPRESSED IN HYPERTROPHIED ADULT FELINE LEFT)

Macroscopic T-type Ca2+ currents, which are often observed in fetal an d neonatal cardiac muscle cells, were not found in normal (0 of 17) ad ult feline ventricular myocytes. However, they were present in most (1 5 of 21) myocytes isolated from adult feline left ventricles with long -standing pressure-overload-induced hypertrophy. This is the first stu dy to provide evidence in a large mammal, such as the cat, that T-type Ca2+ channels may be reexpressed in adults in association with hypert rophy resulting from slow progressive pressure overload. Importantly, this expression was stable for the duration of the hypertrophy process and was not associated with abrupt pressure overload. T-type Ca2+ cur rents were separated from L-type Ca2+ currents by exploiting the diffe rences in their voltage dependence of steady-state inactivation. Depol arizations from -80 mV revealed a rapidly activating inward current th at peaked in magnitude at -30 mV (-1.8+/-0.9 [mean+/-SD] pA/pF) and fu lly inactivated within 100 milliseconds in 15 of 21 hypertrophied myoc ytes studied. Further depolarizations activated progressively less T-t ype Ca2+ current, so that at +10 mV the L-type Ca2+ current predominat ed. In the hypertrophied myocytes that demonstrated both T-type and L- type Ca2+ currents, two distinct peaks occurred in their current-volta ge relations. T-type Ca2+ currents were not evident in any of the 17 n ormal adult feline left ventricular myocytes studied. The purpose of T -type Ca2+ currents in hypertrophy is unclear. However, their presence may make hypertrophied myocardium more prone to spontaneous action po tentials and increase the likelihood for arrhythmias in partially depo larized hypertrophied myocardium.