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Abstract #22703 Published in IGR 11-1
Ca2+-activated Cl- current in retinal arteriolar smooth muscle
McGahon MK; Needham MA; Scholfield CN; McGeown JG; Curtis TMInvestigative Ophthalmology and Visual Science 2009; 50: 364-371
PURPOSE: To characterize the biophysical, pharmacologic, and functional properties of the Ca2+-activated Cl- current in retinal arteriolar myocytes. METHODS: Whole-cell perforated patch-clamp recordings were made from myocytes within intact isolated arteriolar segments. Arteriolar tone was assessed using pressure myography. RESULTS: Depolarizing of voltage steps to -40 mV and greater activated an L-type Ca2+ current (ICa(L)) that was followed by a sustained current. Large tail currents (Itail) were observed on stepping back to -80 mV. The sustained current and Itail reversed close to 0 mV in symmetrical Cl- concentrations. The ion selectivity sequence for Itail was I(-)> Cl-> glucuronate. Outward Itail was sensitive to the Cl- channel blockers 9-anthracene-carboxylic acid (9-AC; 1 mM), 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS; 1 mM), and disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS; 1 mM), but only DIDS produced a substantial (78%) block of inward tail currents at -100 mV. Itail was decreased in magnitude when the normal bathing medium was substituted with Ca2+-free solution or if ICa(L) was inhibited by 1 μM nimodipine. Caffeine (10 mM) produced large transient currents that reversed close to the Cl- equilibrium potential and were blocked by 1 mM DIDS or 100 μM tetracaine. DIDS had no effect on basal vascular tone in pressurized arterioles but dramatically reduced the level of vasoconstriction observed in the presence of 10 nM endothelin-1. CONCLUSIONS: Retinal arteriolar myocytes have I(Cl(Ca)), which may be activated by Ca2+ entry through L-type Ca2+ channels or Ca2+ release from intracellular stores. This current appears to contribute to agonist-induced retinal vasoconstriction.
Dr. M.K. McGahon, Centre for Vision and Vascular Sciences, School of Medicine and Dentistry, The Queen's University of Belfast, Institute of Clinical Sciences, The Royal Victoria Hospital, UK
Classification:
6.11 Bloodflow measurements (Part of: 6 Clinical examination methods)
3.8 Pharmacology (Part of: 3 Laboratory methods)
