title: β-Adrenoceptor/PKA-stimulation, Na(+)-Ca(2+) exchange and PKA-activated Cl(-) currents in rabbit cardiomyocytes: a conundrum.
abstract: Investigations into the functional modulation of the cardiac Na(+)-Ca(2+) 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 (I(NCX)). 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 10mM Ni(2+). In contrast, the PKA-activated Cl(-) current was not sensitive to Ni(2+), when it was activated downstream to the β-adrenoceptors using 10μM forskolin (an adenylyl cyclase activator). When 10μM forskolin was applied under NCX-selective recording conditions, the Ni(2+)-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 Ni(2+)-sensitive current activated via β-adrenoceptor stimulation under recording conditions previously considered selective for I(NCX); (b) downstream activation of PKA does not augment Ni(2+)-sensitive I(NCX), when this is measured under conditions where the Ni(2+)-sensitive PKA-activated Cl(-) current is not present.
authors: Bristol Heart Institute, Cardiovascular Research Laboratories, School of Physiology & Pharmacology, Medical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors: Palash
authors: P
authors: Barman
authors: Stéphanie C M
authors: SC
authors: Choisy
authors: Jules C
authors: JC
authors: Hancox
authors: Andrew F
authors: AF
authors: James
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D009532:Nickel / Q000737:chemistry / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
chemical_list: D018118:Chloride Channels; D011943:Receptors, Adrenergic, beta; D019831:Sodium-Calcium Exchanger; D005576:Colforsin; D009532:Nickel; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol