Calcium Channel

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. 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.