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Arachidonic acid modulation of K V channel kinetics in retinal arteriolar myocytes
Author(s) -
Kur Joanna,
McGahon Mary K.,
Scholfield C. Norman,
McGeown J. Graham,
Curtis Tim M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.937.14
Subject(s) - arachidonic acid , patch clamp , biophysics , chemistry , membrane potential , retinal , kinetics , myocyte , endocrinology , medicine , biology , biochemistry , receptor , enzyme , physics , quantum mechanics
Recent studies have suggested that arachidonic acid (AA) may act as a vasoconstrictor in the brain and retina, but the mechanisms responsible are poorly understood. To address this issue, we examined the effects of AA on ionic currents in retinal vascular myocytes using the whole‐cell perforated patch‐clamp technique. AA (10μM) inhibited membrane currents between ‐20 and +40 mV (reduced from 19.72±4.34 to 1.64±1.88pA/pF at 0mV, n=7; P<0.005; Student's t‐test), although currents were enhanced at potentials positive to +60mV (increased from 87.14±22.02 to 203.53±29.68pA/pF at +100mV; n=7; P<0.005). As a first step in deciphering how AA modulates the membrane current, we isolated the A–type K v current, which in these cells is carried mainly by K v 1.5+K v β1 containing channels (McGahon et al . 2007 Am J Physiol Heart Circ Physiol 292: H1001–8). AA modulated this current in two ways. It accelerated inactivation (control τ 1 =0.037±0.0033ms, τ 2 =0.37±0.064ms and AA τ 1 =0.016±0.0075ms, τ 2 =0.077±0.019ms; P<0.05 and P<0.001; n=8, step to +40mV), and shifted the voltage–dependence of inactivation to more negative potentials (V 0.5control =−38.7±2.06mV and V 0.5AA =−47.99±1.61mV; P<0.001, step to +60mV). This reduced the steady‐state “window” current at physiological membrane potentials. Effects of AA were observed within 30s of exposure and reached maximal effect at 7mins. We conclude that AA may act as a vasoconstrictor in the retinal vasculature by reducing steady–state K v current leading to membrane potential depolarisation and an increased activation of voltage‐gated Ca 2+ channels. Funded by Fight for Sight, UK, Wellcome Trust and JDRF.