title: Effects of tilisolol, a nonselective beta-adrenergic blocker, on the membrane currents of isolated guinea pig ventricular myocytes.
abstract: The effects of tilisolol, a nonselective beta-adrenoceptor blocker, on transmembrane ionic currents were studied in single guinea pig ventricular myocytes by using the whole-cell voltage clamp technique. In the absence of beta-adrenergic stimulation, 10 microM tilisolol, a concentration higher than that used in the clinical therapeutic regimen, did not affect the L-type Ca2+ current (ICa), the inwardly rectifying K+ current (IK1), or the delayed rectifying K+ current (IK). In addition, it did not induce currents through the adenosine triphosphate (ATP)-sensitive K+ channels. However, under the nonselective beta-adrenergic stimulation with 1 microM isoproterenol, 1 microM tilisolol almost completely reversed the agonist-induced increase of IK. The increase of ICa by isoproterenol was blocked only by approximately 30% with tilisolol. We concluded that, at therapeutic concentrations (0.01-0.15 microM), tilisolol is a pure beta-adrenoceptor antagonist that has no direct effects on the transmembrane ionic currents of mammalian ventricular myocytes, such as ICa, IK1, or IK. Comparison of the dose-dependent effects of tilisolol on ICa and IK suggested that tilisolol may selectively inhibit catecholamine-induced increase of IK at the therapeutic concentrations. The virtually selective inhibition of IK, leaving ICa intact, may be favorable to prevent the catecholamine-induced arrhythmia without inhibiting contraction.
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takagi
authors.forename: Y
authors.initials: Y
authors.lastname: Kihara
authors.forename: T
authors.initials: T
authors.lastname: Mitsuiye
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Sasayama
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D015220:Calcium Channels; D007473:Ion Channels; D007546:Isoquinolines; D015221:Potassium Channels; C036593:tilisolol