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전단 스트레스에 의한 심방근세포 커넥신 해미채널의 활성화

Activation of Connexin Hemichannel by Shear Stress in Atrial Myocytes

약학회지 2019년 63권 4호 p.199 ~ 203
김준철 ( Kim Joon-Chul ) - 충남대학교 약학대학

우선희 (  ) - 충남대학교 약학대학

Abstract


Shear stress induces global Ca2+ waves in atrial myocytes and this Ca2+ wave has been shown to be sensitiveto connexin (Cx) channel interventions. In this study, we investigated whether shear stress activates Cx by measuring dyeflux through the Cx channels in rat atrial myocytes. Because the pores of the hemichannels are large enough to permitflux of large molecules up to 1000 MW, we used a Cx channel-permeable dye, Calcein, and a Cx-impermeable dye,Oregon to evaluate Cx-specific activity under shear stress. Application of shear stress (~16 dyn/cm2) using micro-jetapparatus to single atrial cells induced a significant increase in cellular Calcein efflux. The Calcein efflux was largelypotentiated by the use of Ca2+-free external solutions which enhance Cx hemichannel activity. However, it was suppressedby 95% following the pre-treatment of La3+ (2 mM), a gap junction blocker. Pre-exposure to the pannexin inhibitorprobenecid (800 mM) did not alter the calcein efflux under shear stress. In contrast, the Oregon signal was notsignificantly affected by shear stress exposure, suggesting that calcein efflux by shear exposure was not due to nonspecificincrease in membrane permeability. In a monolayer of HL-1 atrial cell culture treated by the external solutions containingCx-permeable Lucifer Yellow dye, cellular dye influx was increased by shear stress. These results suggest that shear stressactivates Cx hemichannels in atrial myocytes.

키워드

Connexin; shear stress; atrial myocytes
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