Role of T-type Ca2+ channel inhibitors in the pacemaker depolarization in rabbit sino-atrial nodal cells.

1. Effects of T-type Ca2+ channel inhibitors, Ni2+ and tetramethrin, on the spontaneous action potentials in rabbit sino-atrial nodal cells were examined. 2. The firing rate of spontaneous activity was 201 +/- 11 beats/min (n = 18). Experiments were performed at 36 degrees C. 3. Ni2+ (10(-5) to 10(-4) M) and tetramethrin (10(-7) to 5 x 10(-5) M) caused a negative chronotropic effect. Both inhibitors did not affect the maximum diastolic potential, and slowed the rate of depolarization during the diastole. 4. In the presence of TTX (10(-7) M), both inhibitors caused a stronger negative chronotropic effect, and hyperpolarized the maximum diastolic potential. The maximum rate of depolarization was enhanced, and the action potential duration (at 50% repolarization) was prolonged. The action potential amplitude was unaffected. Ni2+ had more potent actions than tetramethrin. 5. T-type and other Ca2+ channel inhibitors affected only the late phase of pacemaker potential, resulting in a negative chronotropic effect. 6. These results indicate that T-type Ca2+ channel inhibitors (Ni2+ and tetramethrin) slow the pacemaker depolarization at the late phase (but not at the initial phase), resulting in a negative chronotropic effect in the sino-atrial nodal cells.