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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-6-21
pubmed:abstractText
We investigated the effect of beta-adrenergic stimulation on Na/Ca exchange in whole-cell patch-clamped guinea-pig ventricular myocytes at 37 degrees C. With ion channel and Na/K pump currents blocked, the Na/Ca exchange current (I(Na-Ca) was measured selectively as membrane current inhibited by 10 mM nickel (Ni) during a voltage ramp applied between +80 and -120 mV. Isoprenaline (1 microM) caused an increase in both inward and outward current generated by the Na/Ca exchange, which was prevented by the beta-adrenoceptor blocker propranolol. These data suggest that isoprenaline caused a receptor-mediated up-regulation of Na/Ca exchange activity. Mimicking beta-adrenoceptor activation, either by stimulation of adenylate cyclase with forskolin or by internal dialysis of cells with cyclic AMP (3':5'-cyclic adenosine monophosphate), also increased I(Na-Ca). Using fluorescence Ca measurement, an increase of internal cAMP was shown to increase the rate of transmembrane Ca transport via the Na/Ca exchange. A selective inhibitor of protein kinase A prevented stimulation of Na/Ca exchange by isoprenaline. These data suggest that the underlying mechanism of stimulation was phosphorylation of the Na/Ca exchange protein by protein kinase A. Isoprenaline did not stimulate I(Na-Ca) when experiments were carried out at 20 degrees C, in contrast to the findings at 37 degrees C. Modulation of Na/Ca exchange by the beta-adrenergic pathway may have important physiological consequences for intracellular Ca regulation and electrical activity during hormonal stimulation, or during sympathetic nerve stimulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0031-6768
pubmed:author
pubmed:issnType
Print
pubmed:volume
439
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
822-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10784358-Adenylate Cyclase, pubmed-meshheading:10784358-Adrenergic beta-Agonists, pubmed-meshheading:10784358-Adrenergic beta-Antagonists, pubmed-meshheading:10784358-Animals, pubmed-meshheading:10784358-Calcium, pubmed-meshheading:10784358-Cyclic AMP, pubmed-meshheading:10784358-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:10784358-Electric Conductivity, pubmed-meshheading:10784358-Guinea Pigs, pubmed-meshheading:10784358-Heart Ventricles, pubmed-meshheading:10784358-Isoproterenol, pubmed-meshheading:10784358-Myocardium, pubmed-meshheading:10784358-Nickel, pubmed-meshheading:10784358-Propranolol, pubmed-meshheading:10784358-Receptors, Adrenergic, beta, pubmed-meshheading:10784358-Sodium-Hydrogen Antiporter, pubmed-meshheading:10784358-Temperature, pubmed-meshheading:10784358-Up-Regulation
pubmed:year
2000
pubmed:articleTitle
Stimulation of Na/Ca exchange by the beta-adrenergic/protein kinase A pathway in guinea-pig ventricular myocytes at 37 degrees C.
pubmed:affiliation
Hoffman-La Roche, Pharma Division, Basel, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't