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Science 21 November 2003:
Vol. 302. no. 5649, pp. 1416 - 1418
DOI: 10.1126/science.1089268
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Reports

Abnormal Coronary Function in Mice Deficient in {alpha}1H T-type Ca2+ Channels

Chien-Chang Chen,1,2 Kathryn G. Lamping,4,5,7 Daniel W. Nuno,4,5,7 Rita Barresi,1,2 Sally J. Prouty,1,2 Julie L. Lavoie,4 Leanne L. Cribbs,8 Sarah K. England,2 Curt D. Sigmund,4 Robert M. Weiss,4,7 Roger A. Williamson,6 Joseph A. Hill,9 Kevin P. Campbell1,2,3*

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 {alpha}1H T-type Ca2+ channel ({alpha}13.2-null) have constitutively constricted coronary arterioles and focal myocardial fibrosis. Coronary arteries isolated from {alpha}13.2-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 {alpha}1H T-type Ca2+ channels is essential for normal relaxation of coronary arteries.

1 Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.
2 Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
3 Department of Neurology, University of Iowa, Iowa City, IA 52242, USA.
4 Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
5 Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
6 Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA.
7 Veterans Administration Medical Center, Iowa City, IA 52242, USA.
8 Cardiovascular Institute, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.
9 Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

* To whom correspondence should be addressed. E-mail: kevin-campbell{at}uiowa.edu

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