Activation of the BK(Ca) channel increases outflow facility and decreases trabecular meshwork cell volume

J Ocul Pharmacol Ther. 2009 Aug;25(4):309-14. doi: 10.1089/jop.2008.0133.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: BK(Ca) channel activation increases outflow facility and decreases cell volume suggesting that K(+) efflux regulates TM cell function.

MeSH terms

  • Animals
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / pharmacology
  • Cell Line
  • Cell Size
  • Dose-Response Relationship, Drug
  • Fluoresceins
  • Fluorescent Dyes
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / metabolism*
  • Microscopy, Confocal
  • Nitric Oxide / metabolism*
  • Peptides / pharmacology
  • Swine
  • Time Factors
  • Trabecular Meshwork / drug effects
  • Trabecular Meshwork / metabolism*
  • Triazenes / pharmacology

Substances

  • 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene
  • Benzimidazoles
  • Fluoresceins
  • Fluorescent Dyes
  • KCNMA1 protein, human
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Peptides
  • Triazenes
  • calcein AM
  • NS 1619
  • Nitric Oxide
  • iberiotoxin