Inhibitory effect of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenyl-ethylamino) propane hydrochloride on inward rectifier and delayed rectifier K+ currents in guinea pig ventricular myocytes

AIM: To study the effects of 1-(2,6-dimethylphenoxy)-2-(3, 4-dimethoxypheny l-ethylamino) propane hydrochloride (DDPH) on action potential (AP), inward rectifier K+ current (I-Kl), and delayed rectifier K+ current (I-K) in iso lated guinea pig ventricular myocytes. METHODS: Whole cell patch-clamp reco rding techniques. RESULTS: DDPH 0.1 - 100 mu mol.L-1 decreased 50 % duratio n of action potential (APD(50)) concentration-dependently. APD(50) was shor tened from (493 +/- 58) to (262 +/- 38) ms (n = 7 cells from 5 guinea pigs, P < 0.01) by DDPH 10 mu mol.L-1. However, 90 % duration of action potentia l (APD(90)) was increased by DDPH (>1 mu mol.L-1). At high concentration (> 10 mu mol L-l) DDPH decreased resting membrane potential (RP) and amplitude of action potential (APA). DDPH inhibited tail current of IK( IK tail) con centration-dependently, 46 % at 10 mu mol.L-1 and 78 % at 100 mu mol.L-1. E C50 for DDPH inhibiting I-K was 13.3 (11.6 - 16.7) mu mol.L-1. DDPH also bl ocked I-Kl. DDPH at high concentration (>10 mu mol.L-1) shifted the reverse potential of I-Kl positively. All the effects of DDPH were reversible afte r washout. CONCLUSION: DDPH blocked both I-Kl and I-K current in guinea pig ventricular myocytes.