Muscarinic M2 receptor inhibition of calcium current in rat nucleus tractus solitarius.

The cholinergic system in the central nervous system plays an important role in higher brain functions, through muscarinic receptors. The nucleus tractus solitarius is known to play a major role in the regulation of cardiovascular, respiratory, gustatory, hepatic and swallowing functions. Voltage-dependent Ca2+ channels (VDCCs) serve as crucial mediators of membrane excitability and Ca2+-dependent functions such as neurotransmitter release, enzyme activity and gene expression. The purpose of this study was to investigate the effects of acetylcholine (Ach) on VDCC currents (I(Ca)) in the nucleus tractus solitarius using patch-clamp recording methods. In 68 out of 99 neurons, an application of ACh caused inhibition of N-type and P/Q-type I(Ba) in a concentration-dependent manner. Pretreatments with AF-DX116 (muscarinic M2 receptor antagonist) attenuated the ACh-induced inhibition of I(Ba). Intracellular dialysis of the Galpha(i)-protein antibody also attenuated the ACh-induced inhibition of I(Ba). These results indicate that ACh inhibits N-type and P/Q-type VDCCs via Gi-protein betagamma subunits mediated by M2 receptors in nucleus tractus solitarius.