TY - JOUR T1 - Molecular Pharmacology of Human Ca<sub>v</sub>3.2 T-Type Ca<sup>2+</sup> Channels: Block by Antihypertensives, Antiarrhythmics, and Their Analogs JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 621 LP - 627 DO - 10.1124/jpet.108.145672 VL - 328 IS - 2 AU - Edward Perez-Reyes AU - Amy L. Van Deusen AU - Iuliia Vitko Y1 - 2009/02/01 UR - http://jpet.aspetjournals.org/content/328/2/621.abstract N2 - Antihypertensive drugs of the “calcium channel blocker” or “calcium antagonist” class have been used to establish the physiological role of L-type Ca2+ channels in vascular smooth muscle. In contrast, there has been limited progress on the pharmacology T-type Ca2+ channels. T-type channels play a role in cardiac pacemaking, aldosterone secretion, and renal hemodynamics, leading to the hypothesis that mixed T- and L-type blockers may have therapeutic advantages over selective L-type blockers. The goal of this study was to identify compounds that block the Cav3.2 T-type channel with high affinity, focusing on two classes of compounds: phenylalkylamines (e.g., mibefradil) and dihydropyridines (e.g., efonidipine). Compounds were tested using a validated Ca2+ influx assay into a cell line expressing recombinant Cav3.2 channels. This study identified four clinically approved antihypertensive drugs (efonidipine, felodipine, isradipine, and nitrendipine) as potent T-channel blockers (IC50 &lt; 3 μM). In contrast, other widely prescribed dihydropyridines, such as amlodipine and nifedipine, were 10-fold less potent, making them a more appropriate choice in research studies on the role of L-type currents. In summary, the present results support the notion that many available antihypertensive drugs block a substantial fraction of T-current at therapeutically relevant concentrations, contributing to their mechanism of action. The American Society for Pharmacology and Experimental Therapeutics ER -