Ca(2+)-stimulated adenylyl cyclases regulate the L-type Ca(2+) current in guinea-pig atrial myocytes.

The Journal of Physiology
Thomas Collins, Derek A Terrar

Abstract

Ca(2+)-stimulated adenylyl cyclases (ACs) have recently been shown to play important roles in pacemaking in the sino-atrial node. Here we present evidence that Ca(2+)-stimulated ACs are functionally active in guinea-pig atrial myocytes. Basal activity of an AC in isolated atrial myocytes was demonstrated by the observations that MDL 12,330A (10 μm), an AC inhibitor, reduced L-type Ca(2+) current (I(CaL)) amplitude, while inhibition of phosphodiesterases with IBMX (100 μm) increased I(CaL) amplitude. Buffering of cytosolic Ca(2+) by exposure of myocytes to BAPTA-AM (5 μm) reduced I(CaL) amplitude, as did inhibition of Ca(2+) release from the sarcoplasmic reticulum with ryanodine (2 μm) and thapsigargin (1 μm). [Ca(2+)]i-activated calmodulin kinase II (CaMKII) inhibition with KN-93 (1 μm) reduced I(CaL), but subsequent application of BAPTA-AM further reduced I(CaL). This effect of BAPTA-AM, in the presence of CaMKII inhibition, demonstrates that there is an additional Ca(2+)-modulated pathway (not dependent on CaMKII) that regulates I(CaL) in atrial myocytes. The effects of BAPTA could be reversed by forskolin (10 μm), a direct stimulator of all AC isoforms, which would restore cAMP levels. In the presence of BAPTA-AM, the action...Continue Reading

References

Jan 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·C O BrostromD J Wolff
Aug 1, 1986·Pflügers Archiv : European journal of physiology·J HeschelerW Trautwein
Feb 6, 1970·Biochemical and Biophysical Research Communications·W Y Cheung
Jan 1, 1970·Advances in Biochemical Psychopharmacology·W Y Cheung
Apr 1, 1993·Pflügers Archiv : European journal of physiology·J Petit-JacquesJ Lenfant
Jun 24, 1993·Nature·J P PieroniR Iyengar
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·J Jurevicius, R Fischmeister
Aug 1, 1996·The Journal of Physiology·J HüserL A Blatter
Apr 1, 1997·The American Journal of Physiology·H SunS Nattel
Jan 24, 2002·Nature·Donald M Bers
Feb 18, 2006·The Journal of Physiology·Katherine A SheehanLothar A Blatter
Jun 13, 2006·Journal of Molecular and Cellular Cardiology·Lars S MaierDonald M Bers
Jan 11, 2007·Journal of Microscopy·S Bolte, F P Cordelières
Sep 16, 2008·Journal of Cardiovascular Pharmacology·Dobromir Dobrev, Stanley Nattel

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Citations

Apr 11, 2015·Frontiers in Physiology·Rebecca A Capel, Derek A Terrar
Mar 29, 2014·Frontiers in Pharmacology·Yuejin Wu, Mark E Anderson
Dec 8, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Richard C BondAndrew F James
Jul 26, 2018·International Journal of Molecular Sciences·Tatiana M VinogradovaEdward G Lakatta
Feb 1, 2018·Urolithiasis·Ryan W WalkerKathleen S Hering-Smith
Nov 11, 2014·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Satomi Adachi-Akahane
Dec 4, 2012·Organic & Biomolecular Chemistry·Qiaoling LiuMartin M F Choi
Oct 17, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Rebecca A CapelDerek A Terrar
Aug 28, 2021·International Journal of Molecular Sciences·Tatiana M Vinogradova, Edward G Lakatta

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