title: Altered [Ca2+]i mobilization in diabetic cardiomyocytes: responses to caffeine, KCl, ouabain, and ATP.
abstract: To study the mechanisms mediating intracellular calcium transients involved in diabetic cardiac dysfunction, changes in intracellular calcium concentration ([Ca2+]i) in response to stimulation by caffeine, ouabain, KCl and ATP were studied in single cardiomyocytes (quiescent or electrically-stimulated) isolated from streptozotocin (STZ) diabetic rats. [Ca2+]i was measured by fluorescence microscopy using fura-2. Peak [Ca2+]i response to caffeine (20 mM) and decline of [Ca2+]i (-peak d[Ca2+]i/dt) were decreased in diabetic myocytes. Insulin treatment corrected these depressed [Ca2+]i responses. The data suggest a reduced sarcoplasmic reticulum (SR) calcium content and a depressed Na-Ca exchange activity in diabetic myocytes. Insulin deficiency may play a causal role in these changes. The maximum [Ca2+]i increase in response to ouabain was reduced in diabetic cells while the sensitivity of diabetic myocytes to ouabain was increased. This may be a result of depressed Na-K ATPase and elevated [Na+]i as previously reported. The KCl (12.5-50 mM)-induced [Ca2+]i increase was enhanced in diabetic cells. Caffeine (20 mM) and dichlorobenzamil (DCB, 10 microM) blocked this [Ca2+]i transient to a smaller degree in diabetic cells, but nitrendipine effects were similar in diabetic and control cells. These effects may be due to the increased L-channel activity and altered features, such as different responses to Ca-channel blockers, in diabetes which has previously been reported. The maximum response of [Ca2+]i to exogenous ATP was increased in diabetic cells while the sensitivity remained unchanged. The mechanisms underlying this enhanced response may be similar to the KCl-induced [Ca2+]i changes in diabetes.
authors: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors: J Z
authors: JZ
authors: Yu
authors: G A
authors: GA
authors: Quamme
authors: J H
authors: JH
authors: McNeill
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D016257:Fura-2; D006321:Heart / Q000187:drug effects; D049528:Insulin, Long-Acting / Q000494:pharmacology / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D049528:Insulin, Long-Acting; C041470:3',4'-dichlorobenzamil; D002110:Caffeine; D010042:Ouabain; D011189:Potassium Chloride; D000584:Amiloride; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2