Effects of streptozotocin-induced diabetes on connexin43 mRNA and protein expression in ventricular muscle.
Abnormal QT prolongation with the associated arrhythmias is a significant predictor of mortality in diabetic patients. Gap junctional intercellular communication allows electrical coupling between heart muscle cells. The effects of streptozotocin (STZ)-induced diabetes mellitus on the expression and distribution of connexin 43 (Cx43) in ventricular muscle have been investigated. Cx43 mRNA expression was measured in ventricular muscle by quantitative PCR. The distribution of total Cx43, phosphorylated Cx43 (at serine 368) and non-phosphorylated Cx43 was measured in ventricular myocytes and ventricular muscle by immunocytochemistry and confocal microscopy. There was no significant difference in Cx43 mRNA between diabetic rat ventricle and controls. Total and phosphorylated Cx43 were significantly increased in ventricular myocytes and ventricular muscle and dephosphorylated Cx43 was not significantly altered in ventricular muscle from diabetic rat hearts compared to controls. Disturbances in gap junctional intercellular communication, which in turn may be attributed to alterations in balance between total, phosphorylated and dephosporylated Cx43, might partly underlie prolongation of QRS and QT intervals in diabetic heart.
Howarth
F C
FC
Department of Physiology, United Arab Emirates University, Al Ain, United Arab Emirates. chris.howarth@uaeu.ac.ae
Chandler
N J
NJ
Kharche
S
S
Tellez
J O
JO
Greener
I D
ID
Yamanushi
T T
TT
Billeter
R
R
Boyett
M R
MR
Zhang
H
H
Dobrzynski
H
H
D000818:Animals; D018031:Connexin 43 / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D017629:Gap Junctions / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D018031:Connexin 43; D009124:Muscle Proteins; D012333:RNA, Messenger