Activation of TRPC4 beta by G alpha(i) subunit increases Ca2+ selectivity and controls neurite morphogenesis in cultured hippocampal neuron

Abstract

The ubiquitous transient receptor potential canonical (TRPC) channels function as non-selective, Ca2+-permeable channels. TRPC channels are activated by stimulation of Gag-PLC-coupled receptors. Here, we report that TRPC4/TRPC5 can be activated by G alpha(i). We studied the essential role of G alpha(i), subunits in TRPC4 activation and investigated changes in ion selectivity and pore dilation of the TRPC4 channel,elicited by the G alpha(i2) subunit. Activation of TRPC4 by Gam increased Ca2+ permeability and Ca2+ influx through TRPC4 channels. Co-expression of the muscarinic receptor (M2) and TRPC4 in HEK293 cells induced TRPC4-mediated Ca2+ influx. Moreover, both TRPC4 beta and the TRPC4 beta-G alpha(12) signaling complex induced inhibition of neurite growth and arborization in cultured hippocampal neurons. Cells treated with KN-93, a CaMKII inhibitor, prevented TRPC4- and TRPC4-G alpha(Q205L)(12)-mediated inhibition of neurite branching and growth. These findings indicate an essential role of G alpha(i) proteins in TRPC4 activation and extend our knowledge of the functional role of TRPC4 in hippocampal neurons. (C) 2013 Elsevier Ltd. All rights reserved.