Bisoprolol inhibits sodium current in ventricular myocytes of rats with diastolic heart failure.
1. Changes in sodium currents (I(Na)) in heart failure contribute to cardiac electrophysiological alterations and, thereby, to ventricular arrhythmias. Bisoprolol has anti-arrhythmic effects, but its direct effect on I(Na) in cardiac cells remains unclear. Accordingly, in the present study we investigated the effects of bisoprolol on ventricular I(Na) in diastolic heart failure (DHF) and normal rats. 2. The DHF model was produced by abdominal aortic coarctation for 4 weeks and single ventricular myocytes were isolated by enzymatic dissociation. The electrophysiological actions of bisoprolol on I(Na) currents were investigated using a whole-cell patch-clamp technique. 3. The membrane capacitance of rats in the DHF group was significantly greater than that of the control group and the current-voltage curve was simultaneously shifted downward. Bisoprolol concentration-dependently decreased I(Na) in ventricular myocytes of both groups (at -45 mV), with IC(50) values of 19.53 +/- 0.06 and 40.78 +/- 0.03 micromol/L in the control and DHF groups, respectively. 4. In both groups, the current-voltage curves were shifted upwards, whereas activation potentials, peak currents and reversal potentials showed no significant changes. At -45 mV, the descent ratio of current densities in the DHF group was lower than that of the control group. In both groups, inactivation curves were shifted to more negative potentials, but activation curves and recovery curves were not altered. Changes in the half-inactivation voltage, V(0.5), and the slope of the inactivation curve, S, were similar for both groups. 5. In conclusion, bisoprolol concentration-dependently decreases I(Na) in ventricular myocytes of DHF and normal rats, which could be responsible, at least in part, for its anti-arrhythmic effects.
Tang
Hui-Fang
HF
Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangzhou, China.
Wu
Shu-Lin
SL
Deng
Chun-Yu
CY
Zhang
Wen-Chang
WC
Kuang
Su-Juan
SJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001012:Aorta, Abdominal / Q000601:surgery; D001017:Aortic Coarctation / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017298:Bisoprolol / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003971:Diastole; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D012964:Sodium; D017298:Bisoprolol