Involvement of Src tyrosine kinase and mitogen-activated protein kinase in the facilitation of calcium channels in rat nucleus of the tractus solitarius by angiotensin II

Abstract

It is recognized that brain contains all the components of the renin–angiotensin systems (RAS). The nucleus of the tractus solitarius (NTS) 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 angiotensin II (Ang II) on VDCC currents (I_Ca) in the NTS using patch-clamp recording methods. An application of Ang II caused facilitation of L-type I_Ca in a concentration-dependent manner with an EC₅₀ of 167 nm and a Hill coefficient of 1.73. AT₁ receptor antagonist losartan antagonized the Ang II-induced facilitation of I_Ca. Intracellular dialysis of the Gα_i-protein antibody attenuated the Ang II-induced facilitation of I_Ca. Both Src tyrosine kinase inhibitor and mitogen-activated protein kinase (MAPK) inhibitor attenuated the Ang II-induced facilitation of I_Ca. p38 MAPK inhibitor also attenuated the Ang II-induced facilitation of I_Ca. These results indicate that Ang II facilitates L-type VDCCs via Gα_i-proteins involving Src tyrosine kinase and p38 MAPK kinase mediated by AT₁ receptors in NTS.