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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Allocryptopine produced a blocking effect on the I(to) in cardiac myocytes, which may be an important mechanism in its antiarrhythmic effect.
Li
Y
Y
Electrophysiology of Laboratory, Institute of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
Wang
S
S
Liu
Y
Y
Li
Z
Z
Yang
X
X
Wang
H
H
Wen
Y
Y
Chen
Y
Y
D000465:Algorithms; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D011817:Rabbits
D000889:Anti-Arrhythmia Agents; D001600:Berberine Alkaloids; D024642:Potassium Channels, Voltage-Gated; C109505:allocryptopine