Modulation by nicotine of the ionic currents in guinea pig ventricular cardiomyocytes. Relatively higher sensitivity to IKr and IKl.
The effects of nicotine on the ionic currents in guinea pig cardiomyocytes were investigated using a whole-cell voltage-clamp technique. Nicotine (30 microM to 1 mM) inhibited the ionic currents in a concentration-dependent manner. Nicotine at 30 microM did not affect the Ca2+ current (ICa), but at 300 microM inhibited ICa at 10 mV by 29.3 +/- 2.4% (n = 6, P < .01) and at 1 mM almost blocked the ICa (by approximately 90%, n = 5, P < .001). After 5- to 10-min washout, these responses had 50-70% recovery. The fast time constant (tau f) of the inactivation phase for ICa at 10 mV was not affected, but the slow one (tau s) increased from 35.7 +/- 2.8 to 39.5 +/- 2.4 ms (n = 7) at 300 microM nicotine. Nicotine at 100 microM also inhibited the delayed rectifier K+ current (IK) at 60 mV by 42.7 +/- 3.0% (n = 7, P < .01), and at 30 microM inhibited the inwardly rectifying K+ current (IKl) at -110 mV by 43.0 +/- 2.5% (n = 7, P < .01). The responses to nicotine were not significantly modified by atropine, hexamethonium, and nicotine receptor antagonists (d-tubocurarine and benzoquinonium). The IK is composed of two components for rapidly and slowly activated currents (IKr and IKs). Nicotine markedly decreased the tail current of IKr, but had less or no effect on that of IKs. However, the activation and inactivation kinetics (d infinity and f infinity) for ICa and its activation kinetics (P infinity) for IKr and IKs were not modified. These results suggest that nicotine inhibits the ionic currents with relatively higher sensitivity to IKl and IKr, resulting in modulation of the cardiac functions.
Satoh
Hiroyasu
H
Department of Pharmacology, Division of Molecular and Cellular Biology, Nara Medical University, Kashihara, Nara 634-8521, Japan. hysat@naramed-u.ac.jp
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D027682:Cation Transport Proteins; D004305:Dose-Response Relationship, Drug; D051638:Ether-A-Go-Go Potassium Channels; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007473:Ion Channels / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D016276:Ventricular Function
D020746:Calcium Channels, L-Type; D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; D007473:Ion Channels; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk); D009538:Nicotine