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

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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 (Ca2+) channels are critical for maintaining both contractility and excitability. In the present study, we identified the CaV3.1d mRNA expressed in embryonic day 14 (E14) mouse heart. CaV3.1d is a splice variant of the α1G, T-type Ca2+ channel. Immunohistochemical localization showed expression of α1G Ca2+ channels in E14 myocardium, and staining of isolated ventricular myocytes revealed membrane localization of the α1G channels. Dihydropyridine-resistant inward Ba2+ or Ca2+ 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. Ni2+ blockade discriminates among T-type Ca2+ channel isoforms and is a relatively selective blocker of T-type channels over other cardiac plasma membrane Ca2+ handling proteins. We demonstrate that 100 μmol/L Ni2+ partially blocked α1G currents under physiological external Ca2+. We conclude that α1G T-type Ca2+ channels are functional in midgestational fetal myocardium.