Regulation of CaV3.2 channels by the receptor for activated C kinase 1 (Rack-1)

Abstract

This study describes the interaction between Ca_V3.2 calcium channels and the receptor for activated C kinase 1 (Rack-1), a scaffold protein which has recently been implicated in neuropathic pain. The coexpression of Ca_V3.2 and Rack-1 in tsA-201 cells led to a reduction in the magnitude of whole-cell Ca_V3.2 currents and Ca_V3.2 channel expression at the plasma membrane. Co-immunoprecipitations from transfected cells show the formation of a molecular protein complex between Cav3.2 channels and Rack-1. We determined that the interaction of Rack-1 occurs at the intracellular II-III loop and the C-terminus of the channel. Finally, the coexpression of PKCβII abolished the effect of Rack-1 on current densities. Altogether, our findings show that Rack-1 regulates Ca_V3.2-mediated calcium entry in a PKC-dependent manner.

Keywords: PKC; Pain; Rack-1; T-type channels.