Ang-II-induced Ca(2+) influx is mediated by the 1/4/5 subgroup of the transient receptor potential proteins in cultured aortic smooth muscle cells from diabetic Goto-Kakizaki rats.
Angiotensin-II (Ang-II) exerts many of its vascular effects, including the pathophysiological changes associated with type 2 diabetes, through changes in intracellular calcium concentration [Ca(2+)](i). We sought to clarify the mechanism responsible for Ang-II-induced Ca(2+) influx in cultured aortic VSMC using the Goto-Kakizaki (GK) rat model of type 2 diabetes. Ang-II-induced Ca(2+) influx was blocked by neither VDCC nor c-src inhibition but was sensitive to inositol 1,4,5-trisphosphate receptor inhibition, lanthanide and the diacylglycerol analogue, oleoyl-2-acetyl-sn-glycerol. Since transient receptor potential canonical (TRPC)-3 gene expression was undetectable in both WKY and GK VSMCs and TRPC6 gene and protein expression were significantly down-regulated in GK, we believe the 1/4/5 subgroup of TRPC proteins plays a significant role. Furthermore, in GK VSMC the elevated calcium influx observed was not attributable to increased TRPC expression, but rather an alteration of TRPC activity.
Evans
Jodi F
JF
Vascular Biology Institute, Department of Medicine, Winthrop University Hospital, Mineola, NY 11501, United States.
Lee
Jin Hee
JH
Ragolia
Louis
L
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; D050051:Transient Receptor Potential Channels; C503500:Trpc5 protein, rat; C096351:transient receptor potential cation channel, subfamily C, member 1; D000804:Angiotensin II; D002118:Calcium