Identification of the T-Type Calcium Channel (Ca V 3.1d) in Developing Mouse Heart

Abstract

Abstract —During cardiac development, there is a reciprocal relationship between cardiac morphogenesis and force production (contractility). In the early embryonic myocardium, the sarcoplasmic reticulum is poorly developed, and plasma membrane calcium (Ca 2+ ) channels are critical for maintaining both contractility and excitability. In the present study, we identified the Ca V 3.1d mRNA expressed in embryonic day 14 (E14) mouse heart. Ca V 3.1d is a splice variant of the α1G, T-type Ca 2+ channel. Immunohistochemical localization showed expression of α1G Ca 2+ channels in E14 myocardium, and staining of isolated ventricular myocytes revealed membrane localization of the α1G channels. Dihydropyridine-resistant inward Ba 2+ or Ca 2+ currents were present in all fetal ventricular myocytes tested. Regardless of charge carrier, inward current inactivated with sustained depolarization and mirrored steady-state inactivation voltage dependence of the α1G channel expressed in human embryonic kidney-293 cells. Ni 2+ blockade discriminates among T-type Ca 2+ channel isoforms and is a relatively selective blocker of T-type channels over other cardiac plasma membrane Ca 2+ handling proteins. We demonstrate that 100 μmol/L Ni 2+ partially blocked α1G currents under physiological external Ca 2+ . We conclude that α1G T-type Ca 2+ channels are functional in midgestational fetal myocardium.