Activation of various G-protein coupled receptors modulates Ca2+ channel currents via PTX-sensitive and voltage-dependent pathways in rat intracardiac neurons

In the present study, we examined the ability of several putative neurotransmitters and neuromodulators to modulate voltage-dependent Ca2+ channel currents in adult rat intracardiac neurons. Of 17 compounds tested, acetylcholine (Ach), neuropeptide Y (NPY), norepinephrine (NE), and met-enkephalin (met-Enk) were effective modulators of the Ca2+ currents. The neurotransmitter-induced current inhibition was associated with slow activation kinetics and relief by a strong depolarizing prepulse. Overnight pretreatment of neurons with pertussis toxin (PTX, 500 ng/ml) significantly attenuated the neurotransmitter-induced current inhibition. Heterologous expression of transducin, a known chelator of G-protein beta gamma subunits, almost completely abolished the neurotransmitter-induced current inhibition. Taken together, our data suggest that four different neurotransmitters inhibit the Ca2+ channel currents in adult rat intracardiac neurons via a pathway that is voltage-dependent, membrane-delimited, and utilizes beta gamma subunits released from PTX-sensitive G-proteins. The Ca2+ channel inhibition by non-cholinergic neurotransmitters may play important roles in regulation of neuronal excitability and Ach release at synapses in intracardiac ganglia, thereby contributing to cholinergic control of cardiac functions. (C) 1999 Elsevier Science B.V. All rights reserved.