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(Circulation Research. 2001;88:403.)
© 2001 American Heart Association, Inc.

Cellular Biology

Identification of the T-Type Calcium Channel (Ca_V3.1d) in Developing Mouse Heart

Leanne L. Cribbs, Beverly L. Martin, Elizabeth A. Schroder, Bradley B. Keller, Brian P. Delisle, Jonathan Satin

From the Cardiovascular Institute (L.L.C., B.L.M.), Loyola University Medical Center, Maywood, Ill, and the Departments of Pediatrics (E.A.S., B.B.K.) and Physiology (B.P.D., J.S.), University of Kentucky College of Medicine, Lexington, Ky.

Correspondence to Jonathan Satin, PhD, Department of Physiology, MS-508, University of Kentucky College of Medicine, Lexington, KY 40536-0298. E-mail jsatin1{at}pop.uky.edu

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 Ca_V3.1d mRNA expressed in embryonic day 14 (E14) mouse heart. Ca_V3.1d is a splice variant of the 1G, T-type Ca²⁺ channel. Immunohistochemical localization showed expression of 1G Ca²⁺ channels in E14 myocardium, and staining of isolated ventricular myocytes revealed membrane localization of the 1G 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 1G 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 1G currents under physiological external Ca²⁺. We conclude that 1G T-type Ca²⁺ channels are functional in midgestational fetal myocardium.

Key Words: calcium channel • cardiac development • low-voltage-activated Ca²⁺ channel

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