Voltage-dependent calcium channels (VDCCs) are large (>400 kDa) heteromers which contain, minimally, three core subunits 1, 2/ , in a 1:1:1 stoichiometry1. Expression of VDCC gene products in Xenopus oocytes, or transfected cells shows that the 1 subunits contain the ion channel pore while the auxiliary 2/ and subunits confer optimal cell surface expression and channel kinetics1. Until recently, the only exception to the above paradigm was the skeletal muscle VDCC, which, in addition to the 1, 2/ , core motif, also has an additional tightly associated integral membrane glycoprotein subunit termed 1. Upon co-expression with the 1.1, 2/ 1, 1a subunits of the skeletal muscle VDCC, subunits alter the peak currents, and the kinetics of channel activation and inactivation with the overall effect being a normalisation of currents to those resembling the endogenous channel2. Together, these results suggest that subunits modulate skeletal muscle VDCCs by stabilising their conformation. _x000B_The 4 subunit is specifically localized in the brain, with the 2 and 3 subunits. It shares >60% sequence homology with the 2 and 3 subunits and ~25% sequence homology with the 1 and 5 subunits.
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