R-type Ca2+ channels contribute to fast synaptic excitation and action potentials in subsets of myenteric neurons in the guinea pig intestine

Background R-type Ca2+ channels are expressed by myenteric neurons in the guinea pig ileum but the specific function of these channels is unknown. Methods In the present study, we used intracellular electrophysiological techniques to determine the function of R-type Ca2+ channels in myenteric neurons in the acutely isolated longitudinal muscle-myenteric plexus. We used immunohistochemical methods to localize the Ca(V)2.3 subunit of the R-type Ca2+ channel in myenteric neurons. We also studied the effects of the non-selective Ca2+ channel antagonist, CdCl2 (100 mu mol L-1), the R-type Ca2+ channel blockers NiCl2 (50 mu mol L-1) and SNX-482 (0.1 mu mol L-1), and the N-type Ca2+ channel blocker omega-conotoxin GVIA (CTX 0.1 mu mol L-1) on action potentials and fast and slow excitatory postsynaptic potentials (fEPSPs and sEPSPs) in S and AH neurons in vitro. Key Results Ca(V)2.3 co-localized with calretinin and calbindin in myenteric neurons. NiCl2 and SNX-482 reduced the duration and amplitude of action potentials in AH but not S neurons. NiCl2 inhibited the afterhyperpolarization in AH neurons. omega-conotoxin GVIA, but not NiCl2, blocked sEPSPs in AH neurons. NiCl2 and SNX-482 inhibited cholinergic, but not cholinergic/purinergic, fEPSPs in S neurons. Conclusions and Inferences These data show that R-type Ca2+ channels contribute to action potentials, but not slow synaptic transmission, in AH neurons. R-type Ca2+ channels contribute to release of acetylcholine as the mediator of fEPSPs in some S neurons. These data indicate that R-type Ca2+ channels may be a target for drugs that selectively modulate activity of AH neurons or could alter fast synaptic excitation in specific pathways in the myenteric plexus.