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Hannes Kodal, Michael Weick, Vanessa Moll, Bernd Biedermann, Andreas Reichenbach, Andreas Bringmann; Involvement of Calcium-Activated Potassium Channels in the Regulation of DNA Synthesis in Cultured Müller Glial Cells. Invest. Ophthalmol. Vis. Sci. 2000;41(13):4262-4267.
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purpose. To determine the involvement of Ca2+-activated
K+ channels of big conductance (BK) and of Ca2+ channels in the regulation of DNA synthesis in cultured guinea pig
Müller cells. DNA synthesis was stimulated by elevated
extracellular potassium, by serum, or by epidermal growth factor.
methods. Dissociated retinas from guinea pigs were cultured for 8 days. Just
before confluence was achieved, the cultures were treated with the test
substances in serum-free or serum-containing media. The rates of DNA
synthesis were assessed by a quantitative bromodeoxyuridine
immunoassay. The intracellular Ca2+ concentration was
measured by the fura-2 fluorescence technique.
results. Blocking the BK channels with tetraethylammonium or by iberiotoxin had
no effect at normal extracellular K+ (5.8 mM) but decreased
the rate of DNA synthesis at higher extracellular K+ (10 or
25 mM). Epidermal growth factor-induced DNA synthesis was decreased by
block of BK channels or by application of the Ca2+ channel
blockers nimodipine and flunarizine. Application of epidermal growth
factor elevated the intracellular Ca2+ concentration of
cultured Müller cells. This elevation was diminished by
co-application of iberiotoxin or of flunarizine.
conclusions. The activity of BK channels is necessary for elevated DNA synthesis in
Müller cells when their membranes are depolarized and/or when the
Ca2+ influx into Müller cells is increased by growth
factors. BK channels may contribute to the maintenance of DNA synthesis
by increasing mitogen-induced increase in intracellular
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