Study on bradycardia induced by diltiazem in the rabbit sinoatrial node

Effects of 3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2, 3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) on the membrane currents of rabbit sinoatrial node cells were examined using the double microelectrode voltage clamp technique. The transmembrane slow inward current (Isi) was reduced after 0.5 mumol/l diltiazem perfusion and Isi was nearly completely suppressed by 2.2 mumol/l diltiazem. As to the blockade of Isi, diltiazem revealed a dose-dependent fashion. Diltiazem also produced a slight decrease of both the steady-state current during depolarization and the tail current after repolarization in these concentration ranges, while the hyperpolarization activated current (Ih) was not affected significantly. Furthermore, higher concentration of diltiazem (10 mumol/l) decreased the steady-state outward current amplitude during depolarization, implying that diltiazem might reduce the potassium outward current (Ik). It is concluded that diltiazem suppressed Isi in a use-dependent manner, not surprisingly, but the drug exerted an additional effect of a decrease in Ik of sinoatrial node cells.