Modulation by nicotine of the ionic currents in guinea pig ventricular cardiomyocytes -: Relatively higher sensitivity to IKr and IK1

The effects of nicotine on the ionic currents in guinea pig cardiomyocytes were investigated using a whole-cell voltage-clamp technique. 21 Nicotine (30 muM to 1 mM) inhibited the ionic currents in a concentration-dependent manner. Nicotine at 30 muM did not affect the Ca2+ Current (I-Ca), but at 300 muM inhibited I-Ca at 10 mV by 29.3 +/- 2.4% (n=6, P<.01) and at 1 mM almost blocked the I-Ca (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 I-Ca, 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 muM nicotine. Nicotine at 100 muM also inhibited the delayed rectifier K+ current (10 at 60 mV by 42.7 +/- 3.0% (n=7, P<.01), and at 30 muM inhibited the inwardly rectifying K+ current (I-Kl) 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 I-K is composed of two components for rapidly and slowly activated currents (I-Kr and I-Ks) Nicotine markedly decreased the tail current of I-Ks but had less or no effect on that of I-Ks. However, the activation and inactivation kinetics (d(infinity) and f(infinity)) for I-Ca and its activation kinetics (P-infinity) for I-Kr and I-Ks were not modified. These results suggest that nicotine inhibits the ionic currents with relatively higher sensitivity to I-Kl and I-Kr, resulting in modulation of the cardiac functions. (C) 2002 Elsevier Science Inc. All rights reserved.