Inhibitory effects of DDPH on two components of delayed rectifier potassium current in guinea pig ventricular cells

To study the effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxy-phenyl-ethylamino) propane hydro-chloride (DDPH) on the rapidly activating component (I(Kr)), and the slowly activating component (I(Ks)) of the delayed rectifier potassium current (I(K)) in guinea pig ventricular myocytes.

Whole-cell patch clamp recording techniques.

DDPH (0.1-100 micromol/L) blocked the I(Kr) in a concentration-dependent manner. The IC50 (micromol/L) was 6.1 (95 % confidence limits: 2.8-13.5). IC50 (micromol/L) of DDPH blocking I(Ks) was 12.5 (95 % confidence limits: 4.8-32.2). DDPH (10 micromol/L) did not affect activation time constants and the voltage-dependent activation of both I(Kr) and I(Ks), the half-activation voltage (V1/2, mV) and slope factor (k, mV) were I(Kr): -23.5+/-2.4 and 8.1+/-2.2 [in presence of DDPH, P >0.05, compared with control, V1/2 (-21.7+/-0.8) and k (5.9+/-0.8)]; I(Ks): 27.1+/-0.7 and 16.6+/-0.8 [in presence of DDPH, P >0.05, compared with control, V1/2 (27.0+/-0.8) and k (14.9+/-0.9)]. DDPH slightly increased the deactivation time-constant of I(Kr) ( r) and I(Ks) ( s) at low concentration (<10 micromol/L). The inactivation of I(Kr) was significantly accelerated by DDPH.

DDPH inhibited both I(Kr) and I(Ks). The blockade was not due to its influence on activation, but the process of deactivation. The blocking of I(Kr) by DDPH was further associated with its acceleration the channel inactivation.