Abstract
To elucidate the electrophysiological effect of dicentrine, an alkaloid isolated from Lindera megaphylla, we examined action potential and membrane currents in single cardiac cells. The tight-seal whole cell clamp technique was used. In the current clamp condition, 3 microM dicentrine prolonged rat ventricular action potential duration (APD50) from 38.9 +/- (SEM)9.8 ms to 147.8 +/- 19.7 ms (n = 12) and reduced its maximal rate of depolarization (Vmax) from 220.5 +/- 20.3 V/s to 37.0 +/- 4.0 V/s. The same concentration of quinidine increased APD50 from 42.5 +/- 5.2 ms to 182.8 +/- 15.6 ms (n = 6) and decreased the Vmax from 225.4 +/- 19.5 V/s to 32.2 +/- 3.0 V/s. Voltage clamp study revealed that dicentrine (1 to 100 microM) inhibited the integral of the transient outward current (Ito-I200) dose-dependently with a KD value of 3.0 +/- 0.5 microM. At 50 mV, the suppression of Ito by 3 microM dicentrine was accompanied by shortening of its inactivation time constant from 41.0 +/- 4.9 ms to 18.8 +/- 2.1 ms. V0.5 for the steady state inactivation curve of Ito was shifted from -25.5 +/- 2.8 mV to -40.6 +/- 2.1 mV. Compared to dicentrine, quinidine exerted stronger but the same mode of inhibition of Ito. 4-Aminopyridine, however, blocked Ito without modification of its inactivation time constant. In addition to the inhibition of Ito, the late outward current (Ilo) was significantly reduced by 10 microM each of dicentrine and quinidine to 60.0 +/- 13.3% and 37.5 +/- 6.3%, respectively. 4-Aminopyridine (2 mM) failed to inhibit this current.(ABSTRACT TRUNCATED AT 250 WORDS)
Published Version
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