Of the ten mammalian voltage-gated calcium channels (VGCCs), those belonging to the L-type family have been best studied for
the development of useful therapeutics for hypertension. Other studies on drugs that target the T-type family of VGCCs suggest
that T-type channels might also be relevant to clinically directed modulation of hypertension; however, the selectivity of
one such drug (i.e., mibefradil) has been called into question. CacnaH1 encodes Cav3.2, one of the three T-type channels. Recently, Cacna1H−/− mice were developed to ascertain the normal roles of T-type channels. Cav3.2-null mice possess continually constricted arterioles in the heart. The smooth muscle and arterioles from isolated knockout
mice are able to contract normally in vitro; however, in the presence of acetylcholine (ACh) or other relaxing agents, the
mutant vasculature is unable to relax to the same degree as does wild-type vasculature. Similarly, blocking wild-type T-type
channels prevents ACh-mediated relaxation. These results suggest an important role of T-type channels in normal cardiovascular
function. But is hope for a specific and useful T-type channel–targeted drug premature?
