GABAB receptor inhibition of P-type Ca2+ channels in central neurons

Abstract

P-type Ca2+ channels in cerebellar Purkinje neurons were inhibited by GABA and the GABAB receptor agonist baclofen. Inhibition of P-type Ca2+ channel current involved changes in voltage dependence and kinetics. Baclofen induced a slow phase of activation and altered tail current kinetics, and inhibition could be partly overcome by large depolarizations. These effects were mimicked by internal application of GTP gamma S, which also made the action of baclofen irreversible. In spinal cord neurons, use of selective channel blockers showed that baclofen inhibited both P-type and N-type Ca2+ channels, but not L-type Ca2+ channels; a high threshold current resistant to blockers of P-type, N-type, and L-type channels was also modulated by baclofen. These results show that stimulation of GABAB receptors in central neurons can modulate P-type Ca2+ channels through a G protein-mediated mechanism similar to the one linked to N-type Ca2+ channels.