DDPH inhibited L-type calcium current and sodium current in a single ventricular myocyte of guinea pig

AIM: To investigate the effects of 1-(2, 6-dimethylphenoxy) -2-(3, 4-dimeth oxyphenyl-ethylamino)propane hydrochloride (DDPH) on L-type calcium current (I-Ca) and sodium current (I-Na) , and to compare its inhibitory potency w ith verapamil and mexiletine. METHODS: Whole-cell patch clamp technique was used to record I-Ca and I-Na in a single ventricular myocytes of guinea pi g. RESULTS: (1) DDPH (3 - 300 mu mol . L-1) decreased I-Ca at 0 mV in a con centration-dependent manner with an IC50 value of 28.5 mu mol . L-1 (95 % c onfidence limits: 14.3 - 42.7 mu mol . L-1, n = 8 cells from 8 guinea pigs) . Verapamil (0.3 - 30 mu mol . L-1) reduced I-Ca with an IC50 value of 1.8 mu mol . L-1 (95 % confidence limits: 1.3 - 2.3 mu mol . L-1, n = 6 cells f rom 6 guinea pigs). Mexiletine 100 mu mol . L-1 did not affect I-Ca (n = 5 cells from 5 guinea pigs, P > 0.05). The degree of use-dependent blocking e ffect of DDPH 30 mu mol/L on I-Ca was 58 % +/- 13 % (n = 5 cells from 5 gui nea pigs, P < 0.01) at 1 Hz and 76 % +/- 11 % (n = 5 cells from 5 guinea pi gs, P < 0.01) at 3 Hz. (2) DDPH (20 - 320 mu mol . L-1) could also block I- Na in a concentration-dependent manner with an IC50 value of 89.0 mu mol . L-1(95 % confidence limits: 68.7 - 109.3 mu mol . L-1, n = 9 cells from 9 g uinea pigs). The IC50 value of mexiletine was 32.2 mu mol . L-1 (95 % confi dence limits: 11.7 - 52.7 mu mol . L-1, n = 5 cells from 5 guinea pigs). Ve rapamil at the concentration of 10 mu mol L-l did not affect I-Na (n = 5 ce lls from 5 guinea pigs, P > 0.05). The blocking effect of DDPH 80 mu mol/Lo n I-Na was non use-dependent. CONCLUSION: DDPH exhibited inhibitory effects on both I-Ca and I-Na, but its inhibitory effect on I-Ca was weaker than v erapamil, and on I-Na was weaker than mexiletine.