Identification of the t-type calcium channel (Ca(v)3.1d) in developing mouse heart.
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 alpha1G, T-type Ca(2+) channel. Immunohistochemical localization showed expression of alpha1G Ca(2+) channels in E14 myocardium, and staining of isolated ventricular myocytes revealed membrane localization of the alpha1G 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 alpha1G 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 micromol/L Ni(2+) partially blocked alpha1G currents under physiological external Ca(2+). We conclude that alpha1G T-type Ca(2+) channels are functional in midgestational fetal myocardium.
Cribbs
L L
LL
Cardiovascular Institute, Loyola University Medical Center, Maywood, Ill, USA.
Martin
B L
BL
Schroder
E A
EA
Keller
B B
BB
Delisle
B P
BP
Satin
J
J
D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D005318:Fetal Heart / Q000737:chemistry; D014644:Genetic Variation; D006321:Heart / Q000196:embryology*; D006352:Heart Ventricles / Q000737:chemistry; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D009206:Myocardium / Q000737:chemistry / Q000166:cytology; D009532:Nickel / Q000494:pharmacology; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D020747:Calcium Channels, T-Type; D012333:RNA, Messenger; D009532:Nickel