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.
Satoh
H
H
Department of Pharmacology, Nara Medical University, Japan.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003864:Depression, Chemical; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009532:Nickel / Q000494:pharmacology; D011722:Pyrethrins / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D009467:Neuromuscular Depolarizing Agents; D011722:Pyrethrins; D013779:Tetrodotoxin; D009532:Nickel; C009424:tetramethrin