Electrophysiological effects of protopine in cardiac myocytes: inhibition of multiple cation channel currents.

摘要: Protopine (Pro) from Corydalis tubers has been shown to have multiple actions on cardiovascular system, including anti-arrhythmic, anti-hypertensive and negative inotropic effects. Although it was thought that Pro exerts its through blocking Ca(2+) currents, the electrophysiological profile of is unclear. The aim this study elucidate ionic mechanisms effects in heart. In single isolated ventricular myocytes guinea-pig, extracellular application markedly reversibly abbreviates action potential duration, decreases rate upstroke (dV/dt)(max), amplitude overshoot a dose-dependent manner. Additionally, produces slight, but significant hyperpolarization resting membrane potential. at 25, 50 100 microM reduces L-type current (I(Ca,L)) 89.1, 61.9 45.8% control, respectively, significantly slows decay kinetics I(Ca,L) higher concentration. steady state inactivation shifted negatively by 5.9 - 7.0 mV (at Pro), whereas voltage-dependent activation remains unchanged. contrast, no evident T-type (I(Ca,T)). presence Pro, both inward rectifier (I(K1)) delayed (I(K)) potassium currents are variably inhibited, depending concentrations. Sodium (I(Na)), recorded low [Na(+)](o) (40 mM) solution, more potently suppressed Pro. At 25 microM, attenuated I(Na) most test voltages (-60 approximately +40 mV, with 53% reduction -30 mV. Thus, not selective channel antagonist. Rather, acts as promiscuous inhibitor cation I(Ca,L), I(K), I(K1) well I(Na). These findings may provide some mechanistic explanations for therapeutic