title: Modulation of beta-adrenergic responses of chloride and calcium currents by external cations in guinea-pig ventricular cells.
abstract: 1. The catecholamine-induced Cl- current and the Ca2+ current were recorded in the single ventricular cells of guinea-pig hearts, using the whole-cell patch clamp technique combined with internal perfusion. Dependence of the beta-adrenergic responses on external monovalent cations was investigated. The Cl- current was recognized by measuring the reversal potential of the agonist-induced current. 2. The amplitude of the Cl- current, activated by 1 microM adrenaline or 0.01-0.1 microM isoprenaline, was decreased when the external Na+ concentration ([Na+]o) was reduced by replacement with Tris+. The conductance of the catecholamine-induced Cl- current was proportional to the logarithm of the [Na+]o over a range of 15-140 mM. When the conductance was plotted against the concentration of Tris+, a dose-dependent inhibition of the Cl- response by Tris+ was suggested with a half-maximum concentration of 95 mM. 3. The inhibitory effect of the Na+ substitute TEA+ on the Cl- current was not affected by either increasing the buffer for the internal Ca2+ (10 mM BAPTA) or for the pH (50 mM HEPES). 4. In the relationship between agonist concentration and the Cl- conductance, the half-maximum concentration (K1/2) of isoprenaline was 0.013 microM in the control Na+ solution, and was shifted to 0.07, 0.08, 0.1 and 0.3 microM in the Li+, Cs+, TEA+ and Tris+ external solutions, respectively. The maximum slope conductance was not significantly affected, except for a slight depression on the Tris+ solution. When the current was induced by adrenaline, qualitatively the same finding was obtained; K1/2 was 0.15 and 3.2 microM in the Na+ and Tris+ solutions, respectively. 5. As a substitute for the external Na+, sucrose seemed to be inert. The activation of the inward Cl- current was conserved in the 300 mM sucrose solution ([Cl-]o = 8 mM) with a K1/2 value of 0.015 microM isoprenaline. 6. The Cl- current, when activated by either an external application of forskolin (0.2-10 microM) or an internal perfusion of cyclic AMP (100-500 microM), was not affected by replacing external Na+ with other cations. Activation of the Cl- current by 0.2-5 microM histamine was also insensitive to a substitution of Na+. These findings indicate that the inhibition by the Na+ substitute is at a point before the activation of GTP-binding protein. 7. The effects of Na+ substitution were not affected by varying the Na+ concentration (0-115 mM) in the internal solution, excluding an involvement of a change in the [Na+]i.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: F M
authors.initials: FM
authors.lastname: Tareen
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Ono
mesh_terms: D000818:Animals; D000252:Calcium-Transporting ATPases; D002412:Cations / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D016623:Ion Pumps / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology; D014325:Tromethamine / Q000494:pharmacology
chemical_list: D002412:Cations; D002712:Chlorides; D016623:Ion Pumps; D011943:Receptors, Adrenergic, beta; D014325:Tromethamine; D013395:Sucrose; D012964:Sodium; D000252:Calcium-Transporting ATPases; D007545:Isoproterenol; D004837:Epinephrine