Murine ventricular L-type Ca(2+) current is enhanced by zinterol via beta(1)-adrenoceptors, and is reduced in TG4 mice overexpressing the human beta(2)-adrenoceptor

British Journal of Pharmacology
J F HeubachU Ravens

Abstract

1. The functional coupling of beta(2)-adrenoceptors (beta(2)-ARs) to murine L-type Ca(2+) current (I(Ca(L))) was investigated with two different approaches. The beta(2)-AR signalling cascade was activated either with the beta(2)-AR selective agonist zinterol (myocytes from wild-type mice), or by spontaneously active, unoccupied beta(2)-ARs (myocytes from TG4 mice with 435 fold overexpression of human beta(2)-ARs). Ca(2+) and Ba(2+) currents were recorded in the whole-cell and cell-attached configuration of the patch-clamp technique, respectively. 2. Zinterol (10 microM) significantly increased I(Ca(L)) amplitude of wild-type myocytes by 19+/-5%, and this effect was markedly enhanced after inactivation of Gi-proteins with pertussis-toxin (PTX; 76+/-13% increase). However, the effect of zinterol was entirely mediated by the beta(1)-AR subtype, since it was blocked by the beta(1)-AR selective antagonist CGP 20712A (300 nM). The beta(2)-AR selective antagonist ICI 118,551 (50 nM) did not affect the response of I(Ca(L)) to zinterol. 3. In myocytes with beta(2)-AR overexpression I(Ca(L)) was not stimulated by the activated signalling cascade. On the contrary, I(Ca(L)) was lower in TG4 myocytes and a significant reduction of single-ch...Continue Reading

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Citations

Apr 8, 2006·Naunyn-Schmiedeberg's Archives of Pharmacology·Dana S HutchinsonTore Bengtsson
Jan 27, 2004·Biochemical and Biophysical Research Communications·Ferdi GronerStefan Herzig
May 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ravi C BalijepalliTimothy J Kamp
Nov 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·Katharina FoersterStefan Herzig
May 25, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Scott A GrandySusan E Howlett
Sep 27, 2005·Physiological Reviews·Nina Wettschureck, Stefan Offermanns
Feb 8, 2007·The Journal of Pharmacology and Experimental Therapeutics·Dennis RottlaenderStefan Herzig
Jan 27, 2017·American Journal of Physiology. Cell Physiology·Kelvin Rozier, Vladimir E Bondarenko
May 20, 2003·The Journal of Biological Chemistry·Marian B MeyersGlenn I Fishman
Aug 23, 2020·Cells·Martin C MichelPeter Hein

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