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

Calcium channels are important targets for therapeutics, but their molecula r diversity complicates characterization of these channels in native heart cells. In this study, we identify a new splice variant of a low-voltage act ivated, or T-type Ca2+, channel in murine atrial myocytes. To date, alpha 1 G and alpha 1H are the only 2 T-type Ca2+ channel isoforms found in cardiov ascular tissue. We compared alpha 1G and alpha 1H channel current heterolog ously 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 depe ndence of activation and inactivation as alpha 1G and alpha 1H. The cloned T-type channels and AT-1 T-type current share similar kinetics of macroscop ic inactivation and deactivation. The kinetics of recovery from inactivatio n of T-type currents serves as an electrophysiological signature for T-chan nel isoform. alpha 1G and AT-1 I-T have a similar recovery from inactivatio n time course that is faster than that for alpha 1H. In all cases, T-type c urrent recovers with a biexponential time course, and the relative amplitud e of fast and slow time courses explains the slower alpha 1H recovery kinet ics, rather than differences in the time constants of the individual transi tions. Thus, the T-type channels may be an important contributor to automat icity in heart cells, and molecular diversity is reflected in the pathway o f recovery from inactivation.