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 betagamma 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 betagamma 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.