Effect of α-Allocryptopine on Transient Outward Potassium Current in Rabbit Ventricular Myocytes

Abstract

Objective: To investigate the mechanism of α-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 µM with an IC₅₀ value of 37 ± 8 µM) 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 µM 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 µM 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% (midmyocardium) and 20.1% (endocardium) after expoure to 30 µM allocryptopine.Transmural dispersion of the I_to was reduced from 11.2 ± 1.2 to 4.7 ± 0.6 pA/pF by 30 µM allocryptopine. Conclusion: Allocryptopine produced a blocking effect on the I_to in cardiac myocytes, which may be an important mechanism in its antiarrhythmic effect.

Sanguinaria canadensis: Traditional Medicine, Phytochemical Composition, Biological Activities and Current Uses

“…In guinea pig atria this elevates intracellular Na + , activating the Na + /Ca 2+ exchanger resulting in increased intracellular Ca 2+ levels, a 10 μM dose having a positive inotropic effect [ 181 ]. Protopine acts as a promiscuous cation channel inhibitor in guinea pigs blocking Ca 2+ , K + and Na + ion channels [ 182 ], while allocryptopine blocks K + channels in rabbit ventricular myocytes [ 183 ]. Allocryptopine is more effective than quinidine in preventing induced arrhythmias in rats [ 184 ].…”

Allocryptopine and benzyltetrahydropalmatine block hERG potassium channels expressed in HEK293 cells

“…Both of the drugs have electrophysiological effects that may contribute to the prolongation of the APD. In previous studies [14] , we demonstrated that ALL possesses an inhibition effect on I to in a frequencydependent manner and decreases the transmural gradient of I to . BTHP inhibits the I Kr and the slowly delayed rectifier potassium current (I Ks ) in a frequency-dependent manner.…”

“…In other reports, we demonstrated that the threshold doses of aconitine and calcium chloride that induced ventricular ectopic beats, ventricular tachycardia and ventricular fibrillation in rats were increased by ALL. The electrophysiological measurements of ALL showed a prolongation of APD in the rabbit heart [14,15] . We have also found that ALL exerted an inhibition effect on the transient outward potassium current (I to ) in a frequencydependent manner and decreased the transmural gradient of I to [16] .…”

Exploring the Anti-inflammatory Effects of Protopine Total Alkaloids of Macleaya Cordata (Willd.) R. Br.

“…PRO also attenuates and prevents LPS-induced inflammatory damage via TRL4 and MAPK/NF-kappa B ( 79 , 80 ). Few studies have examined ALL, although some have reported its potential antiarrhythmic activity ( 81 – 83 ). Only one study reported the protective effect of ALL against oxidative stress-induced neuronal damage ( 84 ).…”