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Olaf Strauss, Rita Rosenthal, Dennis Dey, Julia Beninde, Guido Wollmann, Hagen Thieme, Michael Wiederholt; Effects of Protein Kinase C on Delayed Rectifier K+ Channel Regulation by Tyrosine Kinase in Rat Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2002;43(5):1645-1654.
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purpose. Investigation of the regulation of delayed rectifier potassium channels by protein kinases in retinal pigment epithelial (RPE) cells.
methods. Membrane currents of cultured RPE cells were measured in either the perforated-patch or whole-cell configuration of the patch-clamp technique.
results. Different potassium channel blockers from animal venoms (charybdotoxin, hanatoxin, agitoxin, tityustoxin) were used to identify the delayed rectifying outward current in RPE cells as current through potassium channels, mainly composed of Kv1.3 subunits. Extracellular application of a tyrosine kinase blocker, such as genistein (100 μM), lavendustin A (10 μM), or herbimycin A (4 μM), almost completely abolished the delayed rectifier currents. Intracellular application of the tyrosine kinase pp60c-src (30 U/mL) through a patch pipette led to an increase of the delayed rectifier current consistent with an activation of the delayed rectifier channels by src subtype tyrosine kinase. Inhibition (with 1 μM chelerythrine) or activation (with 1 μM phorbol ester PMA) of protein kinase C (PKC) did not change the activity of delayed rectifier channels. Inhibition of PKC also did not change the effect of tyrosine kinase inhibition of delayed rectifier currents. However, in cells with stimulated PKC, inhibition of tyrosine kinase by genistein led to an increase of delayed rectifier currents. Intracellular application of pp60c-src (30 U/mL) in cells with stimulated PKC led to inhibition of delayed rectifier currents.
conclusions. Tyrosine kinase, of the src family, can activate or inhibit delayed rectifier channels composed of Kv1.3 subunits in RPE cells. The activity of PKC determines whether tyrosine kinase activates or inhibits these K+ channels.
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