TY - JOUR
T1 - Identification of the T-type calcium channel (Cav3.1d) in developing mouse heart
AU - Cribbs, Leanne L.
AU - Martin, Beverly L.
AU - Schroder, Elizabeth A.
AU - Keller, Bradley B.
AU - Delisle, Brian P.
AU - Satin, Jonathan
PY - 2001/3/2
Y1 - 2001/3/2
N2 - 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. Inmmunohistochemical 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 cartier, 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.
AB - 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. Inmmunohistochemical 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 cartier, 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.
KW - Calcium channel
KW - Cardiac development
KW - Low-voltage-activated Ca channel
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U2 - 10.1161/01.RES.88.4.403
DO - 10.1161/01.RES.88.4.403
M3 - Article
C2 - 11230107
AN - SCOPUS:0035793925
SN - 0009-7330
VL - 88
SP - 403
EP - 407
JO - Circulation Research
JF - Circulation Research
IS - 4
ER -