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Clinical and experimental pharmacology & physiology

Attenuation of store-operated Ca2+ entry and enhanced expression of TRPC channels in caudal artery smooth muscle from Type 2 diabetic Goto-Kakizaki rats.


PMID 20337661

Abstract

1. Previously, we found that Ca(2+) entry from the extracellular space via alpha(1)-adrenoceptor-activated, Ca(2+)-permeable channels, but not voltage-gated Ca(2+) channels, is impaired in endothelium-denuded caudal artery smooth muscle from Type 2 diabetic Goto-Kakizaki (GK) rats. In the present study, we investigated the impairment of Ca(2+) entry mechanisms via Ca(2+)-permeable channels from the extracellular space in response to alpha(1)-adrenoceptor stimulation (cirazoline) in endothelium-denuded caudal artery strips isolated from GK rats. 2. The contraction of caudal artery strips from GK rats in response to the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid (10 micromol/L), which causes depletion of Ca(2+) stores and subsequent store-operated Ca(2+) (SOC) entry, was significantly depressed compared with that of Wistar rats (maximal force 0.023 +/- 0.004 vs 0.058 +/- 0.005 mN/mg tissue wet weight, respectively). These results suggest that receptor-activated Ca(2+) entry through SOC channels is impaired in caudal artery smooth muscle in GK rats. 3. The classic transient receptor potential (TRPC) channels, which constitute SOC and receptor-operated cation channels, play an important role in Ca(2+) regulation. Therefore, we investigated the mRNA and protein expression of TRPC channels in caudal artery smooth muscle from Wistar and GK rats using reverse transcription-polymerase chain reaction and immunoblotting. 4. Expression of TRPC1, TRPC3 and TRPC6 mRNA and protein was found in Wistar rats. However, in GK rats, in addition to the expression of these TRPC channels, mRNA and protein expression of TRPC4 was found. The expression of TRPC1 and TRPC6, but not TRPC3, was increased approximately twofold in GK rats compared with Wistar rats. 5. These results suggest that changes in TRPC channel expression may be responsible, in part, for the dysfunction of receptor-mediated Ca(2+) entry in caudal artery smooth muscle of GK rats.

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C223
Cirazoline hydrochloride, solid
C13H16N2O · HCl