Downregulation of K(+) channel genes expression in type I diabetic cardiomyopathy.
Type I diabetic cardiomyopathy has consistently been shown to be associated with decrease of repolarising K(+) currents, but the mechanisms responsible for the decrease are not well defined. We investigated the streptozotocin (STZ) rat model of type I diabetes. We utilized RNase protection assay and Western blot analysis to investigate the message expression and protein density of key cardiac K(+) channel genes in the diabetic rat left ventricular (LV) myocytes. Our results show that message and protein density of Kv2.1, Kv4.2, and Kv4.3 are significantly decreased as early as 14 days following induction of type I diabetes in the rat. The results demonstrate, for the first time, that insulin-deficient type I diabetes is associated with early downregulation of the expression of key cardiac K(+) channel genes that could account for the depression of cardiac K(+) currents, I(to-f) and I(to-s). These represent the main electrophysiological abnormality in diabetic cardiomyopathy and is known to enhance the arrhythmogenecity of the diabetic heart. The findings also extend the extensive list of gene expression regulation by insulin.
Qin
D
D
Department of Veterans Affairs, New York Harbor Healthcare System, Brooklyn Campus, Brooklyn, New York, 11209, USA.
Huang
B
B
Deng
L
L
El-Adawi
H
H
Ganguly
K
K
Sowers
J R
JR
El-Sherif
N
N
D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051669:Shab Potassium Channels; D051672:Shal Potassium Channels
D051668:Delayed Rectifier Potassium Channels; D007328:Insulin; C496988:KCNB1 protein, human; C497018:KCND2 protein, human; C497021:KCND3 protein, human; C496991:Kcnb1 protein, rat; C497020:Kcnd2 protein, rat; C497023:Kcnd3 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D051672:Shal Potassium Channels