title: The role of K+ and Cl- channels in the regulation of retinal arteriolar tone and blood flow.
abstract: OBJECTIVE
  This study tested the role of K(+) and Cl(-) channels in the regulation of retinal blood flow.
  
  
  METHODS
  Studies were carried out in adult Male Hooded Lister rats. Selectivity of ion-channel blockers was established using electrophysiological recordings from smooth muscle in isolated arterioles under voltage clamp conditions. Leukocyte velocity and retinal arteriolar diameter were measured in anesthetized animals using leukocyte fluorography and fluorescein angiography imaging with a confocal scanning laser ophthalmoscope. These values were used to estimate volumetric flow, which was compared between control conditions and following intravitreal injections of ion channel blockers, either alone or in combination with the potent vasoconstrictor Endothelin 1 (Et1).
  
  
  RESULTS
  Voltage-activated K(+) current (IKv) was inhibited by correolide, large conductance (BK) Ca(2+)-activated K(+) current (IKCa) by Penitrem A, and Ca(2+)-activated Cl(-) current (IClCa) by disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS). Intravitreal injections (10 μL) of DIDS (estimated intraocular concentration 10 mM) increased flow by 22%, whereas the BK-blockers Penitrem A (1 μM) and iberiotoxin (4 μM), and the IKv-inhibitor correolide (40 μM) all decreased resting flow by approximately 10%. Endothelin 1 (104 nM) reduced flow by approximately 65%. This effect was completely reversed by DIDS, but was unaffected by Penitrem A, iberiotoxin, or correolide.
  
  
  CONCLUSIONS
  These results suggest that Cl(-) channels in retinal arteriolar smooth muscle limit resting blood flow and play an obligatory role in Et1 responses. K(+)-channel activity promotes basal flow but exerts little modifying effect on the Et1 response. Cl(-) channels may be appropriate molecular targets in retinal pathologies characterized by increased Et1 activity and reduced blood flow.
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Institute of Clinical Sciences, The Royal Victoria Hospital, Belfast, Northern Ireland.
authors.forename: Maurice
authors.initials: M
authors.lastname: Needham
authors.forename: Mary K
authors.initials: MK
authors.lastname: McGahon
authors.forename: Peter
authors.initials: P
authors.lastname: Bankhead
authors.forename: Tom A
authors.initials: TA
authors.lastname: Gardiner
authors.forename: C Norman
authors.initials: CN
authors.lastname: Scholfield
authors.forename: Tim M
authors.initials: TM
authors.lastname: Curtis
authors.forename: J Graham
authors.initials: JG
authors.lastname: McGeown
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology*; D001783:Blood Flow Velocity / Q000502:physiology*; D018118:Chloride Channels / Q000378:metabolism*; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009887:Ophthalmoscopy; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D012161:Retinal Artery / Q000502:physiology*
chemical_list: D018118:Chloride Channels; D015221:Potassium Channels
keywords: ion channels; retinal arterioles; retinal blood flow; smooth muscle