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 (1 100 mol·L^–1) in time-, concentration-, voltage-, and specifically frequency-dependent fashion. The IC₅₀ value for blockade ofI _Kr was 13.5 mol·L^–1, while the IC₅₀ value for blockade of I _Ks was 9.3 mol·L^–1. BTHP 30.0 mol·L^–1 reduced I _Kr and I _Kr,tail by 31 ± 4.3% and 36 ± 4.7% (n = 6, p < 0.01) and decreased I _Ks and I _Ks,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.