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

Collins, T; Terrar, D

Journal article

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

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 actions of IBMX were reduced. In addition, inclusion of cAMP in the patch electrode in the whole-cell configuration prevented the effects of BAPTA. These effects are all consistent with a role for Ca(2+)-stimulated AC in the regulation of atrial myocyte I(CaL).

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APA Style

Collins, T., & Terrar, D. (2012). Ca(2+)-stimulated adenylyl cyclases regulate the L-type Ca(2+) current in guinea-pig atrial myocytes. Journal of Physiology, 590(Pt 8), 1881–1893.

MLA Style

Collins, T, and D Terrar. “Ca(2+)-Stimulated Adenylyl Cyclases Regulate the L-Type Ca(2+) Current in Guinea-Pig Atrial Myocytes.” Journal of Physiology, vol. 590, no. Pt 8, 2012, pp. 1881–93.

Chicago Style

Collins, T, and D Terrar. 2012. “Ca(2+)-Stimulated Adenylyl Cyclases Regulate the L-Type Ca(2+) Current in Guinea-Pig Atrial Myocytes.” Journal of Physiology 590 (Pt 8): 1881–93.
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