Electrophysiological basis for the antiarrhythmic action and positive inotropy of HA-7, a furoquinoline alkaloid derivative, in rat heart

British Journal of Pharmacology
M J SuS C Kuo

Abstract

1. HA-7, a new synthetic derivative of furoquinoline alkaloid, increased the contractile force of right ventricular strips and effectively suppressed the ischaemia-reperfusion induced polymorphic ventricular tachyrhythmias in adult rat heart (EC50 = 2.8 microM). 2. In rat ventricular myocytes, HA-7 concentration-dependently prolonged the action potential duration (APD) and decreased the maximal rate of rise of the action potential upstroke (Vmax). The action potential amplitude and resting membrane potential were also reduced, but to a smaller extent. The prolongation of APD by HA-7 was prevented by pretreating the cells with 1 mM 4-AP. 3. Voltage clamp experiments revealed that HA-7 decreased the maximal current amplitude of I(Na) (IC50 = 4.1 microM) and caused a negative shift of its steady-state inactivation curve and slowed its rate of recovery from inactivation. The use-dependent inhibition of I(Na) by HA-7 was enhanced at a higher stimulation rate. The L-type Ca2+ current (I(Ca)) was also reduced, but to a lesser degree (IC50 = 5.3 microM, maximal inhibition = 31.8%). 4. This agent also influenced the time- and voltage-dependent K currents. The prolongation of APD was associated with an inhibition of a 4-AP sensitive tran...Continue Reading

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Citations

Apr 27, 2005·Biochemical and Biophysical Research Communications·Kun-Ta YangKe-Li Tsai
Oct 1, 2013·The Journal of Biological Chemistry·Linda Tzu-Ling TsengMing-Fu Chang

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