α1-adrenoceptor stimulation increases intracellular pH and Na+ via Na+-H+ exchange in guinea pig papillary muscle

Kim, Jin-sang

Korean Journal of Veterinary Research 1995;35(2):229-236.

α₁-adrenoceptor stimulation increases intracellular pH and Na⁺ via Na⁺-H⁺ exchange in guinea pig papillary muscle

Jin-sang Kim

College of Veterinary Medicine, Chonbuk National University

기니픽 유두근에서 α₁-adrenoceptor 자극에 의한 세포내 pH와 Na⁺ 증가는 Na⁺-H⁺ 교환기를 경유

김진상

전북대학교 수의과대학

Abstract

The effect of ${alpha}_1$-adrenoceptor(${alpha}_1$-AR) stimulation on intracellular pH($pH_i$), $Na^+$ activity($a_{Na}{^i}$) and contractility were investigated in isolated papillary muscles of euthyroid or hyperthyroid guinea pig with conventional microelectrode, $Na^+$ or $H^+$-selective microelectrodes, and tension transducer. Stimulation of the ${alpha}_1$-AR by phenylephrine produced a decrease in $a_{Na}{^i}$ in euthyroid preparations. This decrease in $a_{Na}{^i}$ was abolished in presence of PKC activator, phorbol dibutyrate, and increased contrary to decrease. Phenylephrine also increased $a_{Na}{^i}$ in hyperthyroid ones. However, phenylrephtine produced an increase in $pH_i$ in both euthyroid and hyperthyroid ones. These changes were blocked by prazosin, an antagonist of ${alpha}_1$-AR. These findings suggest that the changes in $a_{Na}{^i}$ and $pH_i$ are mediated by a stimulation of $Na^+-H^+$ exchange via ${alpha}_1$-AR stimulation. This study focused on the increase in $a_{Na}{^i}$, $pH_i$ and contractility. The increase in $pH_i$ was blocked by amiloride or EIPA, $Na^+-H^+$ exchange inhibitors. Therefore, the increase in $a_{Na}{^i}$ and $pH_i$ mediated by ${alpha}_1$-AR appeared to be due to an influx of $Na^+$ and a reduction of $H^+$ through $Na^+-H^+$ exchange. This study also revealed that the increase in $pH_i$ and $a_{Na}{^i}$ might be related to the sustained positive inotropic response. The $a_{Na}{^i}$ increase may contribute to the intracellular $Ca^{2+}$ through the $Na^+-Ca^{2+}$ exchange, and the $pH_i$ increase could cause an increase in the $Ca^{2+}$ sensitivity of myofilaments and may augment the ${alpha}_1$-AR-mediated positive inotropic response.

Key Words: ${alpha}_1$-adrenoceptor, intracellular pH, intracellular sodium activity, phenylephrine, $Na^+-H^+$ exchange