Premium
Blocking effect of carvedilol, a beta‐blocker on Na + /Ca 2+ exchange current in isolated cardiac ventricular cells of guinea pig
Author(s) -
Watanabe Yasuhide,
Kimura Junko
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.718.3
Subject(s) - carvedilol , myocyte , chemistry , metoprolol , ouabain , medicine , guinea pig , channel blocker , patch clamp , pharmacology , biophysics , heart failure , electrophysiology , calcium , biology , sodium , organic chemistry
Background Carvedilol has a 1, b 1, and b 2 ‐adrenergic blocking effects together with the effects such as vasodilating, anti‐ischemic, anti‐oxidant, anti‐apoptotic, anti‐proliferate and anti‐inflammatory activities. Carvedilol inhibited I Kr , I Ks , I Ca‐L and I to in rabbit cardiac ventricular myocytes. On the other hand, metoprolol, a nonselective b‐blocker also has blocking several channels, including I K1 , I Ca and I to in hearts. Murayama et al. (2013) reported that carvedilol and its analogues inhibit delayed after depolarizations (DADs) in Langendorff‐perfused rabbit hearts. It is well known that DADs are caused by the Na + /Ca 2+ exchange current (I NCX ). Methods We examined the effects of carvedilol and metoprolol, two b‐blockers, on I NCX by using the whole‐cell voltage‐clamp method in isolated guinea pig ventricles and CCL39 fibroblast cells expressing dog cardiac Na + /Ca 2+ exchanger (NCX1). Results Carvedilol suppressed I NCX in a concentration‐dependent manner but metoprolol did not in isolated guinea pig cardiac ventricular myocytes. IC 50 values for the Ca 2+ influx (outward) and efflux (inward) components of I NCX were 69.7 μM and 61.5 μM, respectively. Carvedilol at 100 μM inhibited I NCX in CCL39 cells expressing wild type NCX1 similarly to mutant NCX1 without the intracellular regulatory loop. Carvedilol at 30 μM abolished ouabain‐induced DADs in isolated cardiac ventricular myocytes. Conclusions Carvedilol suppressed bi‐directional I NCX in a concentration‐dependent manner with the IC 50 value of approximately 65 μM. We conclude that carvedilol inhibits NCX1 at supratherapeutic concentrations.