title: Effects of nicotine on spontaneous activity and underlying ionic currents in rabbit sinoatrial nodal cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, Nara Medical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Satoh
mesh_terms: 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
chemical_list: D015220:Calcium Channels; D018722:Nicotinic Agonists; D015221:Potassium Channels; D009538:Nicotine; D002118:Calcium