Original Article

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

Authors: Ning ZHONG, Qi-Zhi FANG, Yi ZHANG, Jing-Sheng XIA, Jian-Qing QIAN, Zhao-Nian ZHOU

Abstract

AIM: 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.
METHODS: Whole-cell patch clamp recording techniques.
RESULTS: 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.
CONCLUSIONS: 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.
Keywords:

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