Opening of the voltage-dependent Ca2+ channels permits influx of Ca2+ across the plasma membrane, triggering diverse physiological processes. These channels are widely distributed in the cardiovascular system, constituting the main route for Ca2+ entry essential for excitation and contraction. Ten unique α1 subunits, grouped in 3 families (CaV1, CaV2, and CaV3), that encode the low-voltage–activated T-type and the high-voltage–activated L-, N-, P/Q- and R-type Ca2+ channels, have been identified.1,2 L-type Ca2+ channels are predominantly expressed in the hearts and peripheral vasculature and serve as the preferred molecular target of the initial Ca2+ channel antagonists in the treatment of hypertension.3 Recently, a growing body of evidence has accumulated depicting important roles of T-type Ca2+ channels in the regulation of cardiovascular function, such as generation of pacemaker potential and regulation of arterial resistance.3,4 T-type Ca2+ channels are found in various cell types, including neurons, cardiomyocytes, vascular smooth muscle cells, and endocrine cells, where they participate in a variety of physiological processes, such as low-threshold Ca2+ spike generation, action potential firing, pacemaking, impulse conduction, maintenance of myogenic tone, cell proliferation, and hormone secretion.1 In addition to their predominant role in the regulation of vascular function, T-type Ca2+ channels are also involved in cardiomyocyte growth and survival.3 T-type Ca2+ channel blockers are capable of interrupting certain pathological hypertrophic signaling pathways, including calcineurin-mediated nuclear factor of activated T cells–3 activation.1 The importance of voltage-dependent Ca2+ channels is demonstrated by the clinical efficacy of Ca2+ channels blockers in certain disease conditions, as well as the widespread distribution and function of these channels.1 Three classes of chemically distinct L-type Ca2+ channel blockers have been widely used clinically depending on their biophysical and conformation-dependent interactions …