Glucagon activates Ca2+ and Cl- channels in rat hepatocytes

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dc.contributor.authorAromataris, E.
dc.contributor.authorRoberts, M.
dc.contributor.authorBarritt, G.
dc.contributor.authorRychkov, G.
dc.date.issued2006
dc.descriptionThe definitive version is available at www.blackwell-synergy.com
dc.description.abstractGlucagon is one of the major hormonal regulators of glucose metabolism, counteracting the hepatic effects of insulin when the concentration of glucose in the bloodstream falls below a certain level. Glucagon also regulates bile flow, hepatocellular volume and membrane potential of hepatocytes. It is clear that changes in cell volume and membrane potential cannot occur without significant ion fluxes across the plasmamembrane. The effects of glucagon onmembrane currents in hepatocytes, however, are not well understood. Here we show, by patch-clamping of rat hepatocytes, that glucagon activates two types of currents: a small inwardly rectifying Ca2+ current with characteristics similar to those of the store-operated Ca2+ current and a larger outwardly rectifying Cl− current similar to that activated by cell swelling. We show that the mechanism of glucagon action on membrane conductance involves phospholipase C and adenylyl cyclase. Contribution of the adenylyl cyclase-dependent pathway to activation of the currents depended on Epac (exchange protein directly activated by cAMP), but not on protein kinase A. The activation of Ca2+ and Cl− channels is likely to play a key role in the mechanisms by which glucagon regulates hepatocyte metabolism and volume.
dc.description.statementofresponsibilityEdoardo C. Aromataris, Michael L. Roberts, Greg J. Barritt and Grigori Y. Rychkov
dc.identifier.citationThe Journal of Physiology, 2006; 573(3):611-625
dc.identifier.doi10.1113/jphysiol.2006.109819
dc.identifier.issn0022-3751
dc.identifier.issn1469-7793
dc.identifier.orcidAromataris, E. [0000-0001-7238-5833]
dc.identifier.orcidRychkov, G. [0000-0002-2788-2977]
dc.identifier.urihttp://hdl.handle.net/2440/24041
dc.language.isoen
dc.publisherBlackwell Publishing Ltd
dc.source.urihttps://doi.org/10.1113/jphysiol.2006.109819
dc.subjectCells, Cultured
dc.subjectCell Membrane
dc.subjectHepatocytes
dc.subjectAnimals
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectChlorides
dc.subjectCalcium
dc.subjectPyrrolidinones
dc.subjectAdenine
dc.subjectEstrenes
dc.subjectGlucagon
dc.subjectCalcium Channels
dc.subjectChloride Channels
dc.subjectReceptors, Glucagon
dc.subjectCyclic AMP
dc.subjectCalcium Channel Agonists
dc.subjectProtein Kinase Inhibitors
dc.subjectPatch-Clamp Techniques
dc.subjectIon Channel Gating
dc.subjectTime Factors
dc.subjectMale
dc.subjectType C Phospholipases
dc.subjectChloride Channel Agonists
dc.subjectAdenylyl Cyclases
dc.subjectAdenylyl Cyclase Inhibitors
dc.titleGlucagon activates Ca2+ and Cl- channels in rat hepatocytes
dc.typeJournal article
pubs.publication-statusPublished

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