Abnormal Coronary Function in Mice Deficient in α 1H T-type Ca 2+ Channels

Abstract

Calcium ion (Ca ²⁺ ) influx through voltage-gated Ca ²⁺ channels is important for the regulation of vascular tone. Activation of L-type Ca ²⁺ channels initiates muscle contraction; however, the role of T-type Ca ²⁺ channels (T-channels) is not clear. We show that mice deficient in the α _1H T-type Ca ²⁺ channel (α ₁ 3.2-null) have constitutively constricted coronary arterioles and focal myocardial fibrosis. Coronary arteries isolated from α 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 Ni ²⁺ prevented relaxation of wild-type coronary arteries. Thus, Ca ²⁺ influx through α _1H T-type Ca ²⁺ channels is essential for normal relaxation of coronary arteries.