Diabetes modulates capacitative calcium entry and expression of transient receptor potential canonical channels in human saphenous vein.
Diabetes is associated with a perturbation of signaling pathways in vascular tissue, which causes vasomotor dysfunction such as hypertension. We have previously demonstrated that vessels from diabetic patients were more contractile than those from non-diabetic. However, in human vessels, the receptor-stimulated contraction is mainly due to enzymatic, rather than calcium signaling pathway. In this study, we hypothesized that the differential contractile response between diabetic and non-diabetic human vessels could be due to the receptor signaling to sarcoplasmic reticulum and the regulation of capacitative calcium entry. In saphenous vein samples (n=20) collected from diabetic patients undergoing bypass surgery, the contraction initiated by the addition of the sarco-endoplasmatic reticulum calcium ATPase blocker, cyclopiazonic acid, was significantly higher than that in the vessels from non-diabetic patients (n=26) (84.0+/-14.9% vs 44.2+/-9.2%), and this contraction was inhibited by SKF-96365, an inhibitor of store-operated calcium channels. Pre-incubation with indomethacin reduced the cyclopiazonic acid-induced contraction in the non-diabetic veins, but had no effect on the diabetic ones. The gene expression of transient receptor potential canonical channels (TRPC)4 was upregulated by 22% in the diabetic vessels compared with the non-diabetic ones. However, the protein expression of TRPC1 and TRPC6 was downregulated in the diabetic group by 50%. We concluded that diabetes would modulate the capacitative calcium entry likely through the store-operated calcium channel specifically via the regulation of TRPC.
Chung
Ada W Y
AW
The James Hogg iCAPTURE Center for the Cardiovascular and Pulmonary Research, St Paul's Hospital, Vancouver, British Columbia, Canada. adawingyee@yahoo.ca
Au Yeung
Karen
K
Chum
Elliott
E
Okon
Elena B
EB
van Breemen
Cornelis
C
D000368:Aged; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D025802:Electric Capacitance; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D007211:Indoles; D050052:TRPC Cation Channels; D002118:Calcium; C000543:cyclopiazonic acid