Inhibitory effects of dauricine on potassium currents in guinea pig ventricular myocytes

AIM: To study the effects of dauricine(Dau) an the rapidly activating compo nent (I-Kr), the slowly activating component (I-Ks) Of the delayed rectifie r potassium: current, and the inward rectifier potassium current ( I-K1 ) i n guinea pig ventricular myocytes. METhODS: Single myocytes were dissociate d by enzymatic dissociation method. The currents were recorded with the who le-cell configuration of the patch-clamp technique. RESULTS: (1) Dau 1, 3, 10, 30, and 100 mu mol.L-1 blocked I-Kr and tail current (IKr-tail) in a co ncentration-dependent manner. The IC50 for block of IKr-tail was 16 (95 % c onfidence limits: 13 - 22) mu mol.L-1 The time constant of IKr-tail deactiv ation was (140 +/- 38) ms in the control and (130 +/- 26) ms in the presenc e of Dau 30 mu mol.L-1(n = 6 cells from 3 animals, P > 0.05). (2) Dau 1 - 1 00 mu mol.L-1 Produced concentration-dependent blocks of I-Ks and tail The IC50 value for block of IKs-tail was 33 (95 % confidence limits: 24 - 46) m u mol.L-1 The time constant of IKs-tail deactivation was (92 +/- 18) ms in the control and (84 +/- 16) ms in the presence of Dau 30 mu mol.L-1(n = 8 c ells from 4 animals, P > 0.05). (3) Addition of Dau 30 mu mol.L-1 induced b lock of I-Ks and IKs-tail (n = 7 cells from 3 animals). The degree of block of IK, and IKs-tail depended on test potentials, increasing with more posi tive depolarizations. (4) Dau 20 mu mol.L-1 blocked mainly inward component of I-K1 and reduced the reversal potential from -72 mV (control) to - 78 m V ( n = 6 cells from 3 animals). CONCLUSION: (1) Dau inhibited I-Ks, but no t the process of IKs deactivation. (2) Dan blocked I-Kr, but not the proces s of deactivation. (3) Dau had a blocking effect on I-K1.