Role of anions in nitric oxide-induced short-circuit current increase in isolated porcine ciliary processes

Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3213-22. doi: 10.1167/iovs.03-1252.


Purpose: To investigate how nitric oxide (NO) modulates short-circuit current (Isc) in isolated porcine ciliary processes.

Methods: Isc changes (Ussing-type chamber) induced either by the NO donors SNP or SIN-1, or by the cGMP analogue 8-pCPT-cGMP were assessed. The effect of inhibitors of guanylate cyclase (10 microM ODQ, 100 microM LY83583), protein kinase G (30 microM Rp-8-pCPT-cGMP, 3 microM KT 5823), protein kinase A (1 microM KT 5720), or protein kinase C (1 microM Go6983) on SNP- or 8-pCPT-cGMP-induced Isc changes were investigated. The effect of inhibitors of anion channel (100 microM niflumic acid, 1 mM DIDS, and 1 mM 9-AC), K+-channel (10 mM TEA, 10 mM BaCl2), Na+-channel blockers (1 mM amiloride), Na+-K+-2Cl- cotransporter inhibitor (0.5 mM bumetanide), or carbonic anhydrase inhibitor (1 mM acetazolamide) was studied. In Cl(-)- or HCO3(-)-free Krebs-Ringer solution, the effect of SNP- or 8-pCPT-cGMP-induced Isc changes was accessed.

Results: SNP, SIN-1, or 8-pCPT-cGMP increased Isc with a change in the potential difference that became more negative toward the nonpigmented epithelium (aqueous) side. The Isc increase induced by SNP or SIN-1, but not by 8-pCPT-cGMP, was prevented by ODQ and LY83583. SNP- and 8-pCPT-cGMP-induced Isc increases were prevented by Rp-8-pCPT-cGMP or KT5823 (but not by KT5720 or Go6983), or by niflumic acid, DIDS, 9-AC, or acetazolamide (but not by TEA, BaCl2, amiloride, or bumetanide). The effect of SNP and 8-pCPT-cGMP was abolished in Cl(-)- and reduced in HCO3(-)-free solutions.

Conclusions: NO activates a guanylate cyclase-cGMP-protein kinase G pathway that appears to stimulate stroma-to-aqueous anionic transport, possibly Cl-, in porcine ciliary epithelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anion Transport Proteins / metabolism
  • Anions / metabolism*
  • Aqueous Humor / metabolism
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Chloride Channels / antagonists & inhibitors
  • Ciliary Body / physiology*
  • Corneal Stroma / metabolism
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / pharmacology
  • Electric Conductivity
  • Enzyme Inhibitors / pharmacology
  • Guanylate Cyclase / antagonists & inhibitors
  • Ion Exchange
  • Molsidomine / analogs & derivatives
  • Molsidomine / pharmacology
  • Nitric Oxide / physiology*
  • Nitric Oxide Donors / pharmacology
  • Nitroprusside / pharmacology
  • Protein Kinase Inhibitors
  • Swine
  • Thionucleotides / pharmacology


  • Anion Transport Proteins
  • Anions
  • Carbonic Anhydrase Inhibitors
  • Chloride Channels
  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • Protein Kinase Inhibitors
  • Thionucleotides
  • Nitroprusside
  • Nitric Oxide
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-GMP
  • linsidomine
  • Molsidomine
  • Guanylate Cyclase
  • Cyclic GMP