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.
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D006329:Heart Conduction System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D015293:Transducin / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*