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This Article Full Text Full Text (PDF) All Versions of this Article: 573/3/611    most recent jphysiol.2006.109819v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aromataris, E. C. Articles by Rychkov, G. Y. Search for Related Content PubMed PubMed Citation Articles by Aromataris, E. C. Articles by Rychkov, G. Y. Related Collections Cellular

¹ School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia
² Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, South Australia 5001, Australia

Glucagon 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 plasma membrane. The effects of glucagon on membrane 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.

(Received 15 March 2006; accepted after revision 30 March 2006; first published online 31 March 2006)
Corresponding author G. Y. Rychkov: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia. Email: grigori.rychkov{at}adelaide.edu.au

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