Effects of benzyltetrahydropalmatine on two components of the delayed rectifier K+ current in guinea pig ventricular myocytes

The effects of benzyltetrahydropalmatine (BTHP), a new class III antiarrhythmic agent, on the action potential in guinea pig papillary muscle and the rapidly activating component (I-Kr) and the slowly activating component (I-Ks) of the delayed rectifier potassium current (I-K) in isolated guinea pig ventricular myocytes were investigated. The action potentials of papillary muscles were studied using a standard microelectrode technique, while the K+ currents were recorded using the whole-cell patch clamp technique. The results showed that BTHP prolonged the action potential duration (APD) without altering other variables of the action potential in guinea pig papillary muscles. The 2 components of I-K were blocked by BTHP (1 similar to 100 mumol.L-1) in time-, concentration-, voltage-, and specifically frequency-dependent fashion. The IC50 value for blockade of I-Kr was 13.5 mumol.L-1, while the IC50 value for blockade of I-Ks was 9.3 mumol.L-1. BTHP 30.0 mumol.L-1 reduced I-Kr and I-Kr,I-tail by 31 +/- 4.3% and 36 +/- 4.7% (n = 6, p < 0 01) and decreased I-Ks and I-Ks,I-tail by 40 ± 6.3% and 39 ± 4.6% (n = 7 p < 0 01) respectively. BTHP accelerated their deactivation course by reducing the time constants of deactivation of I-Kr and I-Ks. The activation kinetics of I-Kr or I-Ks were not affected by BTHP. It is concluded that BTHP prolonged the action potential duration with respect to its non-selective action on I-Kr and I-Ks in single guinea pig ventricular cell in a frequency-dependent fashion.