Abnormal Coronary Function in Mice Deficient in α_1H 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 α_1H T-type Ca²⁺ channel (α₁3.2-null have constitutively constricted coronary arterioles and focal myocardial fibrosis. Coronary arteries isolated from α₁3.2-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 α _1H T-type Ca²⁺ channels is essential for normal relaxation of coronary arteries.