title: Defective intracellular Ca(2+) signaling contributes to cardiomyopathy in Type 1 diabetic rats.
abstract: The goal of the study was to determine whether defects in intracellular Ca(2+) signaling contribute to cardiomyopathy in streptozotocin (STZ)-induced diabetic rats. Depression in cardiac systolic and diastolic function was traced from live diabetic rats to isolated individual myocytes. The depression in contraction and relaxation in myocytes was found in parallel with depression in the rise and decline of intracellular free Ca(2+) concentration ([Ca(2+)](i)). The sarcoplasmic reticulum (SR) Ca(2+) store and rates of Ca(2+) release and resequestration into SR were depressed in diabetic rat myocytes. The rate of Ca(2+) efflux via sarcolemmal Na(+)/Ca(2+) exchanger was also depressed. However, there was no change in the voltage-dependent L-type Ca(2+) channel current that triggers Ca(2+) release from the SR. The depression in SR function was associated with decreased SR Ca(2+)-ATPase and ryanodine receptor proteins and increased total and nonphosphorylated phospholamban proteins. The depression of Na(+)/Ca(2+) exchanger activity was associated with a decrease in its protein level. Thus it is concluded that defects in intracellular Ca(2+) signaling caused by alteration of expression and function of the proteins that regulate [Ca(2+)](i) contribute to cardiomyopathy in STZ-induced diabetic rats. The increase in phospholamban, decrease in Na(+)/Ca(2+) exchanger, and unchanged L-type Ca(2+) channel activity in this model of diabetic cardiomyopathy are distinct from other types of cardiomyopathy.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati, Ohio 45267, USA.
authors.forename: Kin M
authors.initials: KM
authors.lastname: Choi
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhong
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hoit
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Grupp
authors.forename: Harvey
authors.initials: H
authors.lastname: Hahn
authors.forename: Keith W
authors.initials: KW
authors.lastname: Dilly
authors.forename: Silvia
authors.initials: S
authors.lastname: Guatimosim
authors.forename: W Jonathan
authors.initials: WJ
authors.lastname: Lederer
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Matlib
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D000199:Actins; D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium