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β-Adrenoceptor/PKA-stimulation, Na+–Ca2+ exchange and PKA-activated Cl− currents in rabbit cardiomyocytes: A conundrum

By Palash Barman, Stéphanie C.M. Choisy, Jules C. Hancox and Andrew F. James

Abstract

Investigations into the functional modulation of the cardiac Na+–Ca2+ exchanger (NCX) by acute β-adrenoceptor/PKA stimulation have produced conflicting results. Here, we investigated (i) whether or not β-adrenoceptor activation/PKA stimulation activates current in rabbit cardiac myocytes under NCX-‘selective’ conditions and (ii) if so, whether a PKA-activated Cl−-current may contribute to the apparent modulation of NCX current (INCX). Whole-cell voltage-clamp experiments were conducted at 37 °C on rabbit ventricular and atrial myocytes. The β-adrenoceptor-activated currents both in NCX-‘selective’ and Cl−-selective recording conditions were found to be sensitive to 10 mM Ni2+. In contrast, the PKA-activated Cl− current was not sensitive to Ni2+, when it was activated downstream to the β-adrenoceptors using 10 μM forskolin (an adenylyl cyclase activator). When 10 μM forskolin was applied under NCX-selective recording conditions, the Ni2+-sensitive current did not differ between control and forskolin. These findings suggest that in rabbit myocytes: (a) a PKA-activated Cl− current contributes to the Ni2+-sensitive current activated via β-adrenoceptor stimulation under recording conditions previously considered selective for INCX; (b) downstream activation of PKA does not augment Ni2+-sensitive INCX, when this is measured under conditions where the Ni2+-sensitive PKA-activated Cl− current is not present

Topics: Article
Publisher: Elsevier
OAI identifier: oai:pubmedcentral.nih.gov:3092849
Provided by: PubMed Central
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