Effect of alpha-allocryptopine on transient outward potassium current in rabbit ventricular myocytes

To investigate the mechanism of alpha-allocryptopine-induced inhibition of the transient outward potassium current (I(to)) in rabbit left-ventricular myocytes.

We used the whole-cell patch-clamp technique to record the I(to) in the myocytes, which were isolated from the rabbit left ventricle by a Langendorff-perfusion device.

Allocryptopine decreased the amplitude and the density of the I(to) in a concentration-dependent (range from 1 to 100 microM with an IC(50) value of 37 +/- 8 microM) and frequency- or use-independent manner. At a test potential of +50 mV, the peak current density of I(to) was decreased from 21.56 +/- 3.24 to 13.37 +/- 2.86 pA/pF by 30 microM allocryptopine. The fast time constant of I(to) inactivation was reduced from 9.8 +/- 1.8 to 5.7 +/- 0.7 ms and the slow time constant of I(to) was reduced from 50.8 +/- 9.0 to 32.2 +/- 12.7 ms by 30 microM allocryptopine. The inactivated curve slope was changed from -19.2 +/- 7.1 to -7.5 +/- 0.6 mV, while the half-activated voltage and activated curve slope and half-inactivated voltage values were not affected by allocryptopine. Transmural heterogeneity of the I(to) was decreased in the presence of allocryptopine. At a test potential of +50 mV, the densities of I(to) were reduced by 28.6% (epimyocardium), 50.3% (mid-myocardium) and 20.1% (endocardium) after exposure to 30 microM allocryptopine.Transmural dispersion of the I(to) was reduced from 11.2 +/- 1.2 to 4.7 +/- 0.6 pA/pF by 30 microM allocryptopine.

Allocryptopine produced a blocking effect on the I(to) in cardiac myocytes, which may be an important mechanism in its antiarrhythmic effect.