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This Article Full Text Full Text (PDF) All Versions of this Article: 555/2/397    most recent jphysiol.2003.057646v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Piper, A. S. Articles by Large, W. A. Search for Related Content PubMed PubMed Citation Articles by Piper, A. S. Articles by Large, W. A.

Department of Basic Medical Sciences, Pharmacology and Clinical Pharmacology, Cardiovascular Research Group, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK

The present study describes the single channel properties of a novel cGMP-activated Ca²⁺-dependent Cl^- channel in rat mesenteric artery smooth muscle cells. Single channel currents were recorded in cell-attached patches in the presence of 8Br cGMP in response to the addition of caffeine or noradrenaline and in both outside-out and inside-out patches when the internal patch surface was bathed in cGMP and Ca²⁺. The channels were permeable to Cl^- ions with an anion permeability sequence of SCN^- (1.7) > Cl^- (1.0) > I^- (0.6). Single channel mean open probability (NP_o) was independent of voltage and the channels displayed three conductance levels of 15, 35 and 55 pS. cGMP was required for channel activation and the single channel NP_o increased sharply with raised [Ca²⁺]_i, maximal activation occurring at a [Ca²⁺]_i of about 100 nM. The relationship between NP_o and cGMP concentration was voltage independent and could be fitted by the Hill equation giving a K_d of about 3 µM and a Hill coefficient (n_H) of 3. cGMP- and Ca²⁺-dependent channel currents were inhibited by 10 µM ZnCl₂ but niflumic acid, an inhibitor of Ca²⁺-activated Cl^- channels, had no effect. Inhibition of cGMP-dependent protein kinase activity by the cGMP-dependent protein kinase inhibitor KT5823 or replacement of ATP by AMP-PNP reduced NP_o, while activation of cGMP-dependent protein kinase by guanosine 3', 5'-cyclic monophosphate, ß-phenyl-1, N²-etheno-8-bromo-sodium salt (8Br PET cGMP) produced a significant increase in single channel NP_o. It is likely that these single channel currents underlie the noradrenaline-activated inward current important for vasomotion in these resistance arteries.

(Received 4 November 2003; accepted after revision 19 December 2003; first published online 23 December 2003)
Corresponding author A. S. Piper: Department of Basic Medical Sciences, Pharmacology and Clinical Pharmacology, Cardiovascular Research Group, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. Email: a.piper{at}sghms.ac.uk

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