Modulation of a voltage-activated potassium channel by peptide growth factor receptors.
Regulation of the activity of a cloned component of a voltage-activated K+ channel, Kv1.5, was studied by expressing the K+ channel and receptors for platelet-derived growth factor (PDGF) or fibroblast growth factor (FGF) simultaneously in Xenopus oocytes. Receptor activation mediated a decline in the Kv1.5 current amplitude, with a half-time of about 20 min. The reduction in K+ current amplitude occurred with little change in the kinetics or voltage sensitivity of activation. A similar phenomenon was found when the human thrombin or rat 5-HT1c receptors, two receptors that increase phospholipase C activity, were tested in coexpression experiments. A mutant FGF receptor, which does not activate phospholipase C-gamma 1 but retains several of its other functions, did not modulate the Kv1.5 current. Simultaneous injection of inositol trisphosphate and superfusion of phorbol 12-myristate 13-acetate reproduced the modulation of the Kv1.5 current. These results demonstrate that the PDGF and FGF receptors can modulate a voltage-activated K+ channel by increasing phospholipase C activity, and suggest that PDGF or FGF may be able to alter rapidly the electrical excitability of neurons.
Timpe
L C
LC
Program of Excellence in Molecular Biology, University of California at San Francisco 94143.
Fantl
W J
WJ
D000818:Animals; D004553:Electric Conductivity / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D051966:Phospholipase C gamma; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism; D014981:Xenopus
D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D015221:Potassium Channels; D017468:Receptors, Fibroblast Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D011188:Potassium