Dismuke William M, Ellis Dorette Z
Department of Pharmacodynamics, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
J Ocul Pharmacol Ther. 2009 Aug;25(4):309-14. doi: 10.1089/jop.2008.0133.
Inhibition of the BK(Ca) channel attenuated the nitric oxide-induced increase in outflow facility and decrease in trabecular meshwork (TM) cell volume suggesting the involvement of the BK(Ca) channel in TM cell function. This study examined the effects of activation of the BK(Ca) channel on outflow facility and TM cell volume and determined if the effects of NO and BK(Ca) channel activation on TM cell volume were additive.
Porcine eyes were used to measure outflow facility using the anterior segment organ culture perfusion system. Cell volume was measured using Calcein AM fluorescent dye, detected by confocal microscopy, and quantified using NIH ImageJ software.
NS1619 increased outflow facility 86% over baseline. Additionally, there was a concentration-dependent decrease in TM cell volume in response to NS1619, which was abolished by iberiotoxin (IBTX). While NS1619 alone and DETA-NO alone decreased TM cell volume, together their effects were not additive. The time course for NS1619-induced increases in outflow facility correlated with the time course for NS1619-induced decreases in cell volume.
BK(Ca) channel activation increases outflow facility and decreases cell volume suggesting that K(+) efflux regulates TM cell function.
抑制大电导钙激活钾通道（BK(Ca)通道）可减弱一氧化氮诱导的房水流出易度增加和小梁网（TM）细胞体积减小，提示BK(Ca)通道参与TM细胞功能。本研究检测了BK(Ca)通道激活对房水流出易度和TM细胞体积的影响，并确定一氧化氮和BK(Ca)通道激活对TM细胞体积的影响是否具有累加性。
使用猪眼，通过眼前节器官培养灌注系统测量房水流出易度。使用钙黄绿素-AM荧光染料测量细胞体积，通过共聚焦显微镜检测，并使用美国国立卫生研究院（NIH）ImageJ软件进行定量分析。
NS1619使房水流出易度比基线增加了86%。此外，NS1619可使TM细胞体积呈浓度依赖性减小，而iberiotoxin（IBTX）可消除这种减小。虽然单独使用NS1619和单独使用DETA-NO均可减小TM细胞体积，但二者共同作用时其效果并无累加性。NS1619诱导的房水流出易度增加的时间进程与NS1619诱导的细胞体积减小的时间进程相关。
BK(Ca)通道激活可增加房水流出易度并减小细胞体积，提示钾离子外流调节TM细胞功能。
