Effects of Nonylphenol on L-type Ca~(2+) Currents in Isolated Guinea-pig Ventricular Myocytes / 中国医科大学学报

Objective To observe the effects of nonylphenol(NP) on L-type Ca~(2+) currents(I_(Ca-L)) in isolated guinea-pig ventricular myocytes.Methods The ventricular myocytes were isolated from guinea-pig hearts.The L-type Ca~(2+) currents in the ventricular myocytes treated with NP were measured with whole cell patch-clamp technique.Results Nonylphenol inhibited lew,at different potentials.Nonylphenol (10~(-6) mol·L~(-1),10~(-5) mol·L~(-1)) reduced the peak amplitude of I_(Ca-L) from-3.2±1.5 pA·pF~(-1) to-1.6±0.8 pA·pF~(-1)(P<0.01) and-1.4±0.7 pA·pF~(-1)(P<0.01),respectively.Nonylphenol did not influence the activation curve of I_(Ca-L) significantly.Conclusion Nonylphenol could in hibit the L-type calcium currents in isolated guinea-pig ventricular myocytes with a concentration-dependent manner.Objective To observe the effects of nonylphenol(NP) on L-type Ca~(2+) currents(I_(Ca-L))in isolated guinea-pig ventricular myocytes.Methods The ventricular myocytes were isolated from guinea-pig hearts.The L-type Ca~(2+) currents in the ventricular myocytes treated with NP were measured with whole cell patch-clamp technique.Results Nonylphenol inhibited lew,at different potentials.Nonylphenol hibit the L-type calcium currents in isolated guinea-pig ventricular myocytes with a concentration-dependent manner.

Fluoxetine inhibits L-type Ca2+ and transient outward K+ currents in rat ventricular myocytes

The most common cardiovascular side effects of antidepressants are cardiac arrhythmias and orthostatic hypotension. Little is known, however, about the mechanisms by which these adverse reactions may occur, especially with regard to newer drugs such as fluoxetine. We hypothesized that these side effects may have an electrophysiological basis at the level of the cardiac myocyte. Thus, we investigated the effects of fluoxetine and other antidepressants on action potentials and ionic currents of rat ventricular myocytes using the amphotericin B perforated patch clamp technique. Fluoxetine (10 microM) prolonged the action potential duration (APD50) to 146.7 +/- 12.9% of control value without altering resting membrane potential. Fluoxetine and sertraline potently inhibited the L-type Ca2+ current (IC50 = 2.82 and 2.31 microM, respectively), but did not significantly modify the steady-state inactivation. Amitriptyline and imipramine had similar, but slightly weaker, effects (IC50 = 3.75 and 4.05 microM, respectively). Fluoxetine attenuated the peak transient outward K+ current and also altered current kinetics, as shown by accelerated decay. Fluoxetine did not change the voltage-dependence of the steady-state inactivation. Sertraline, amitriptyline and imipramine inhibited the transient outward K+ current with potencies very similar to fluoxetine. In contrast to the other antidepressants tested, trazodone weakly inhibited the Ca2+ and K+ currents and moclobemide had no detectable effect. Our comparative pharmacology data suggest that selective serotonin reuptake inhibitors, such as fluoxetine, are as potent as tricyclic antidepressants in inhibiting L-type Ca2+ and transient outward K+ currents. These inhibitory effects may contribute to cardiovascular complications such as arrhythmias and orthostatic hypotension.

Mechanism of arrhythmias caused by autoantibodies against ?_1-adrenoceptors induced by hepatitis B virus in mice / 中国病理生理杂志

AIM: To investigate the significance of autoantibodies against ?_1-adrenoceptors induced by hepatitis B virus in the pathogenesis of hepatitis virus myocarditis. METHODS: 30 mice were injected peritoneally with an emulsion of hepatitis B virus and complete Freund's adjuvant every three weeks. The autoantibodies were examined by ELISA, the heart and liver specimens were collected on 56 d for pathological observation and the binding of the autoantibodies to guinea pig cardiac myocytes were examined by immunofluorescence. Using the patch clamp technique, the effects of (1∶50) autoantibodies purified by octanoic acid extraction on the action potential and L type Ca~(2+) currents of guinea pig cardiac myocytes were also investigated. RESULTS: There was a good correlation between the autoantibodies and hepatitis B virus. Without pathological changes in the heart and liver specimens, 6 mice of the test group manifested bundle branch block, sinus arrest and premature ventricular beat etc, which were positive in the autoantibodies. The specific binding of the autoantibodies of the mice to guinea pig cardiac myocytes was observed. (1∶50) autoantibodies of the mice prolonged APD_(20), APD_(50), APD_(90) by 36.46%, 29.63% and 12.40%, respectively and enhanced L type Ca~(2+) currents by (49.67?16.01)%. CONCLUSIONS: Autoantibodies against ?_1-adrenoceptors of the mice induced by hepatitis B virus result in several arrhythmias, which might be mediated by the enhancement of L type Ca~(2+) currents.