Abnormal coronary function in mice deficient in alpha1H T-type Ca2+ channels.
Calcium ion (Ca2+) influx through voltage-gated Ca2+ channels is important for the regulation of vascular tone. Activation of L-type Ca2+ channels initiates muscle contraction; however, the role of T-type Ca2+ channels (T-channels) is not clear. We show that mice deficient in the alpha1H T-type Ca2+ channel (alpha(1)3.2-null) have constitutively constricted coronary arterioles and focal myocardial fibrosis. Coronary arteries isolated from alpha(1)3.2-null arteries showed normal contractile responses, but reduced relaxation in response to acetylcholine and nitroprusside. Furthermore, acute blockade of T-channels with Ni2+ prevented relaxation of wild-type coronary arteries. Thus, Ca2+ influx through alpha1H T-type Ca2+ channels is essential for normal relaxation of coronary arteries.
Chen
Chien-Chang
CC
Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.
Lamping
Kathryn G
KG
Nuno
Daniel W
DW
Barresi
Rita
R
Prouty
Sally J
SJ
Lavoie
Julie L
JL
Cribbs
Leanne L
LL
England
Sarah K
SK
Sigmund
Curt D
CD
Weiss
Robert M
RM
Williamson
Roger A
RA
Hill
Joseph A
JA
Campbell
Kevin P
KP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D004452:Echocardiography; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D005355:Fibrosis; D005727:Ganglia, Spinal / Q000166:cytology; D018390:Gene Targeting; D006321:Heart / Q000502:physiology; D006339:Heart Rate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D020747:Calcium Channels, T-Type; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D009532:Nickel; D000109:Acetylcholine; D002118:Calcium