Impact of gating modulation in CaV1.3 L-type calcium channels

Ca(V)1.3 L-type channels control inner hair cell (IHC) sensory and sinoatrial node (SAN) function, and excitability in central neurons by means of their low-voltage activation and inactivation properties. In SAN cells Ca(V)1.3 inward calcium current (I-Ca) inactivates rapidly whereas in IHCs inactivation is slow. A candidate suggested in slowing Ca(V)1.3 channel inactivation is the presynaptically located ribbon-synapse protein RIM that is expressed in immature IHCs in presynaptic compartments also expressing Ca(V)1.3 channels. Ca(V)1.3 channel gating is also modulated by an intramolecular C-terminal mechanism. This mechanism was elicited during analysis of human C-terminal splice variants that differ in the length of their C-terminus and that modulates the channel's negative activation range and slows calcium-dependent inactivation.