Mechanisms of Cyclovirobuxine D on APD Prolongation in Rat Ventricular Myocytes

Abstract

Abstract: Aim To study the effects of cyclovirobuxine D on inward rectifier K⁺ current (IK1), transient outward K⁺ current (Ito), L-type Ca²⁺ current (ICa-L), and action potential duration (APD) in isolated rat ventricular myocytes.Methods The whole cell patch-clamp techniques were used to study the changes of IK1, Ito, ICa-L and APD in rat ventricular myocytes. Results Cyclovirobuxine D (1-10 μmol·L^-1) significantly prolonged APD50 and APD90 in isolated rat ventricular myocytes. Resting potential (RP) was decreased by 10 μmol·L^-1 of cyclovirobuxine D. Cyclovirobuxine D significantly decreased both inward and outward components of IK1. At - 100 mV, 1 and 10 μmol·L^-1 of cyclovirobuxine D decreased IK1 density from (-8.0±1.1) pA/pF to (-4.1±0.7) pA/pF and (-3.4±0.8) pA/pF, respectively,whereas at - 30 mV, IK1 density was decreased from (1.10±0.24) pA/pF to (0.61±0.18) pA/pF and (0.36±0.11)pA/pF, respectively. IIto was markedly inhibited by cyclovirobuxine D from the test potential of 0 mV to + 60 mV. At + 40 mV, 1 and 10 μmol·L^-1 of cyclovirobuxine D decreased Ito density from (8.9±2.0) pA/pF to (5.5±1.2) pA/pF and (4.9 + 0.9) pA/pF, respectively. Cyclovirobuxine D inhibited ICa-L in a concentration-dependent manner. At 10 mV, 1 and 10 μmol·L^-1 of cyclovirobuxine D decreased ICa-L density from (-9.9±1.8) pA/pF to (-6.4±1.4) pA/pF and (-4.2±0.6) pA/pF, respectively. Conclusion Cyclovirobuxine D significantly prolonged APD and inhibited IK1, Ito and ICa-L in rat ventricular myocytes. The inhibitory effects of cyclovirobuxine D on IK1 and Ito are major molecular mechanisms of APD prolongation in rat.

Key words: cyclovirobuxine D, cyclovirobuxine D, cardiomyocytes, cardiomyocytes, ion channels, ion channels, APD, APD, potassium channels, potassium channels, L-type ca2+ current, L-type ca2+ current

CLC Number:

R285

R331.3⁺8

Supporting:

CHEN Qing-wen, SHAN Hong-li, WANG He, LI Zhe, YANG Bao-feng^*. Mechanisms of Cyclovirobuxine D on APD Prolongation in Rat Ventricular Myocytes[J]. .

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