Roles of a1 and a1/b Subunits Derived from Cardiac L-Type Ca Channels on Voltage-Dependent Facilitation Mechanisms

diac calcium (Ca) channel plays a crucial role in excitation–contraction coupling in cardiac and other muscles. The cardiac Ca channel comprises four subunits: a1, b, and a2/d. The pore-forming a1 subunit involves the most important functional elements of the L-type Ca channel, including a selectivity filter, a voltage sensor, a motif for Ca-dependent inactivation, and a binding site for dihydropyridines (DHPs) [1–3]. The functional role of the a2/d subunit is less clear; some investigators [4, 5] have reported that it modifies the a1 subunit function; thus the activation times of the barium current could be reduced 50%. Others claim that the a2/d subunit plays a role in the acceleration of current activation and inactivation [6]. The cardiac a1 subunit current, generated by interactions with or without specific b subunits, has been studied with a variety of expression systems. A homologous coexpression of the cardiac a1 subunit (a1C) with the cardiac b subunit (b2a) increased both the amplitude of the Ba current and the rate of channel activation [7, 8]. A coexpression of the cardiac a1 subunit (a1C) with the skeletal b subunit (b1) similarly increased the density of the L-type Ca current [4, 5] and increased the rate of inactivation [4, 9]. Moreover, Ca currents of cardiac a11a2 subunit combinations were increased in the presence of the brain/cardiac b subunit (b3) [8]. These findings suggest that although their structures are different, b1, b2, and b3 subunits play similar regulatory roles in the kinetic modulation of channel openings by interacting with the a1 subunit.