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Modulation of beta‐adrenergic responses of chloride and calcium currents by external cations in guinea‐pig ventricular cells.
Author(s) -
Tareen F M,
Yoshida A,
Ono K
Publication year - 1992
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1992.sp019374
Subject(s) - chemistry , tris , bapta , isoprenaline , conductance , hepes , calcium , reversal potential , endocrinology , patch clamp , medicine , analytical chemistry (journal) , chromatography , biochemistry , receptor , mathematics , organic chemistry , combinatorics , stimulation
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)