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 neurotran smitters and neuromodulators to modulate voltage-dependent Ca2+ channel cur rents in adult rat intracardiac neurons. Of 17 compounds tested, acetylchol ine (Ach), neuropeptide Y (NPY), norepinephrine (NE), and met-enkephalin (m et-Enk) were effective modulators of the Ca2+ currents. The neurotransmitte r-induced current inhibition was associated with slow activation kinetics a nd relief by a strong depolarizing prepulse. Overnight pretreatment of neur ons with pertussis toxin (PTX, 500 ng/ml) significantly attenuated the neur otransmitter-induced current inhibition. Heterologous expression of transdu cin, a known chelator of G-protein beta gamma subunits, almost completely a bolished the neurotransmitter-induced current inhibition. Taken together, o ur data suggest that four different neurotransmitters inhibit the Ca2+ chan nel currents in adult rat intracardiac neurons via a pathway that is voltag e-dependent, membrane-delimited, and utilizes beta gamma subunits released from PTX-sensitive G-proteins. The Ca2+ channel inhibition by non-cholinerg ic neurotransmitters may play important roles in regulation of neuronal exc itability and Ach release at synapses in intracardiac ganglia, thereby cont ributing to cholinergic control of cardiac functions. (C) 1999 Elsevier Sci ence B.V. All rights reserved.