Effects of nicotine on spontaneous activity and underlying ionic currents in rabbit sinoatrial nodal cells.
1. Effects of nicotine on the spontaneous action potentials and the underlying ionic currents in rabbit sinoatrial (SA) nodal cells were investigated using current-clamp and whole-cell voltage-clamp modes. 2. Nicotine (30 microM to 1 mM) produced a negative chronotropic effect in a concentration-dependent manner (at 1 mM by 10.6 +/- 2.8%, n = 9, p < 0.01). Nicotine at 300 microM significantly decreased the maximum rate of depolarization by 9.8 +/- 1.3% (n = 9, p < 0.05). Other action potential parameters were not affected to any significant extent. 3. Pretreatment with atropine (1 microM) and hexamethonium (1 mM) did not modify the nicotine-induced effects. After washout, these responses were reversible. 4. Isoprenaline decreased the responses induced by nicotine, but ACh increased them. 5. Nicotine at 100 microM did not affect the L-type Ca2+ current (ICa), but at 300 microM inhibited it at + 10 mV by 21.6 +/- 2.9% (n = 6, p < 0.05). The fast time constant (tau f) of the inactivation phase for ICa was not affected, but the slow one (tau s) significantly increased from 36.8 +/- 1.9 ms to 41.2 +/- 2.8 ms (n = 6) at 300 microM nicotine. The activation and inactivation kinetics (d infinity and f infinity) for ICa were not modified. 6. Nicotine also did not affect the delayed rectifier K+ current (IK) and its activation kinetic (P infinity). 7. These results suggest that nicotine depresses the action potentials and causes a negative chronotropic effect due to inhibitions of the ionic currents in the SA nodal cells.
Satoh
H
H
Department of Pharmacology, Nara Medical University, Japan.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D015220:Calcium Channels; D018722:Nicotinic Agonists; D015221:Potassium Channels; D009538:Nicotine; D002118:Calcium