title: High glucose concentration causes a rise in [Ca2+]i of cardiac myocytes.
abstract: Diabetes mellitus is associated with an elevation in the basal levels of cytosolic calcium ([Ca2+]i) of cardiac myocytes. This may be due in part to a glucose-induced elevation in [Ca2+]i. The present study examined this issue and explored the cellular pathways responsible for such a phenomenon. A total of 30 mM glucose, mannitol or choline chloride, but not urea, induced a time- and dose-dependent rise in the [Ca2+]i of cardiac myocytes. G protein inhibition by GDP beta S or pertussis toxin produced significant inhibition (> or = 80%) in the rise in [Ca2+]i. Incubation of cardiac myocytes in a calcium free medium or in media containing verapamil, nifedipine or amlodipine almost completely abolished the rise in [CA2+], while ryanodine produced only small reduction (10%) in the glucose-induced rise in [Ca2+]i. Rp-cAMP or H-89, inhibitors of the cAMP-protein kinase A pathway, produced a modest decrease in the rise in [Ca2+]i, while staurosporine (an inhibitor of PKC) and HOE 694 (an inhibitor of the Na(+)-H+ exchanger) had no effect on the rise in [Ca2+]i. The results indicate that the osmotic activity of glucose (cell shrinkage) activates G protein(s), most likely through a stretch receptor, which in turn stimulates calcium channels inhibitable by verapamil, nifedipine and amlodipine, thus permitting a calcium influx into the cardiac myocytes. The increased calcium entry may stimulate a calcium release from intracellular stores by a calcium-induced calcium release process. Thus, in cardiac myocytes direct activation of calcium channels, and to a small extent activation of the cAMP-protein kinase A, and calcium-induced calcium release mediate the high glucose-induced acute rise in their [Ca2+]i.
authors.affiliation: Division of Nephrology, University of Southern California School of Medicine, Los Angeles, USA.
authors.forename: M
authors.initials: M
authors.lastname: Smogorzewski
authors.forename: V
authors.initials: V
authors.lastname: Galfayan
authors.forename: S G
authors.initials: SG
authors.lastname: Massry
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D005947:Glucose; D002118:Calcium