Referenced in: none

Automatically associated channels: Cav2.1 , Cav3.1 , Cav3.2

Title: Down-regulation of endogenous KLHL1 decreases voltage-gated calcium current density.

Authors: Paula P Perissinotti, Elizabeth G Ethington, Leanne Cribbs, Michael D Koob, Jody Martin, Erika S Piedras-Rentería

Journal, date & volume: Cell Calcium, 2014 May , 55, 269-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24703904

Abstract
The actin-binding protein Kelch-like 1 (KLHL1) can modulate voltage-gated calcium channels in vitro. KLHL1 interacts with actin and with the pore-forming subunits of Cav2.1 and CaV3.2 calcium channels, resulting in up-regulation of P/Q and T-type current density. Here we tested whether endogenous KLHL1 modulates voltage gated calcium currents in cultured hippocampal neurons by down-regulating the expression of KLHL1 via adenoviral delivery of shRNA targeted against KLHL1 (shKLHL1). Control adenoviruses did not affect any of the neuronal properties measured, yet down-regulation of KLHL1 resulted in HVA current densities ~68% smaller and LVA current densities 44% smaller than uninfected controls, with a concomitant reduction in α(1A) and α(1H) protein levels. Biophysical analysis and western blot experiments suggest Ca(V)3.1 and 3.3 currents are also present in shKLHL1-infected neurons. Synapsin I levels, miniature postsynaptic current frequency, and excitatory and inhibitory synapse number were reduced in KLHL1 knockdown. This study corroborates the physiological role of KLHL1 as a calcium channel modulator and demonstrates a novel, presynaptic role.