Identification of a T-type Ca2+ channel isoform m in murine atrial myocytes (AT-1 cells)

Abstract

Calcium channels are important targets for therapeutics, but their molecular diversity complicates characterization of these channels in native heart cells. In this study, we identify a new splice variant of a low-voltage activated, or T-type Ca2+, channel in murine atrial myocytes. To date, α1G and α1H are the only 2 T-type Ca2+ channel isoforms found in cardiovascular tissue. We compared α1G and α1H channel current heterologously expressed in HEK 293 cells with T-type current from the murine atrial tumor cell, AT-1. AT-1 cell T-type current (I(T)) has the same voltage dependence of activation and inactivation as α1G and α1H. The cloned T-type channels and AT-1 T-type current share similar kinetics of macroscopic inactivation and deactivation. The kinetics of recovery from inactivation of T-type currents serves as an electrophysiological signature for T-channel isoform. α1G and AT-1 I(T) have a similar recovery from inactivation time course that is faster than that for α1H. In all cases, T-type current recovers with a biexponential time course, and the relative amplitude of fast and slow time courses explains the slower α1H recovery kinetics, rather than differences in the time constants of the individual transitions. Thus, the T- type channels may be an important contributor to automaticity in heart cells, and molecular diversity is reflected in the pathway of recovery from inactivation.