Abstract
The cholinergic system in the CNS plays important roles in higher brain functions, through muscarinic receptors. The nucleus tractus solitarius (NTS) is known to plays 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. ACh injected into the NTS of rat elicits a decrease in arterial pressure and heart rate similar to that seen with activation of the baroreflex. The purpose of this study was to investigate the effects of ACh on VDCCs currents (ICa) in the NTS using patch-clamp recording methods. In 68 of 99 neurons, an application of ACh caused inhibition of N- and P/Q-types IBa in a concentration-dependent manner. Application of a strong depolarizing voltage prepulse attenuated the ACh-induced inhibition of IBa. Pretreatments with AF-DX116 (muscarinic M2 receptor antagonist) attenuated the ACh-induced inhibition of IBa. In contrast, Pretreatments with Telenzepine (muscarinic M1 receptor antagonist) did not attenuate the ACh-induced inhibition of IBa. Intracellular dialysis of the Gi-protein antibody also attenuated the ACh-induced inhibition of IBa. In contrast, intracellular dialysis of and Gs- and Gq/11-proteins antibodies did not attenuate the ACh-induced inhibition of IBa. These results indicate that ACh inhibits N- and P/Q-types VDCCs via Gi-protein beta gamma subunits mediated by M2 receptors in NTS. [J Physiol Sci. 2007;57 Suppl:S152]
