ASIC-like Currents in Freshly Isolated Cerebral Artery Smooth Muscle Cells are Inhibited by Endogenous Oxidase Activity

作者：Chung Wen Shuo; Farley Jerry M; Drummond Heather A^*

来源：Cellular Physiology and Biochemistry, 2011, 27(2): 129-138.

DOI：10.1159/000325215

• Extracellular acid gated currents
• Degenerin
• Vascular smooth muscle
• Oxidation-reduction

Background/Aims: The aim of this study was to determine if VSMC ASIC-like currents are regulated by oxidative state. Methods: We used whole-cell patch clamp of isolated mouse cerebral VSMCs to determine if 1) reducing agents, such as DTT and GSH, and 2) inhibition of endogenous oxidase activity from NADPH and Xanthine oxidases potentiate active currents and activate electrically silent currents. Results: Pretreatment with 2 mM OTT or GSH, increased the mean peak amplitude of ASIC-like currents evoked by pH 6.0 from 0.4 +/- 0.1 to 14.9 +/- 3.6 pA/pF, and from 0.9 +/- 0.3 to 11.3 +/- 2.4 pA/pF, respectively. Pretreatment with apocynin, a NADPH oxidase inhibitor, mimics the effect of the reducing agents, with the mean peak current amplitude increased from 0.9 +/- 0.5 to 7.0 +/- 2.6 pA/pF and from 0.5 +/- 0.2 to 26.4 +/- 6.8 pA/pF by 50 and 200 mu M apocynin, respectively. Pretreatment with allopurinol, a xanthine oxidase inhibitor, also potentiates the VSMC ASIC-like activity. Conclusion: These findings suggest that VSMC ASIC-like channels are regulated by oxidative state and may be inhibited by basal endogenous oxidative sources such as NADPH and xanthine oxidase.

• 出版日期2011