Modal behavior of the Kv1.1 channel conferred by the Kvbeta1.1 subunit and its regulation by dephosphorylation of Kv1.1.
Modulation of fast-inactivating voltage-gated K+ channels can produce plastic changes in neuronal signaling. Previously, we showed that the voltage-dependent K+ channel composed of brain Kv1.1 and Kvbeta1.1 subunits (alpha(beta) channel) gives rise to a current that has a fast-inactivating and a sustained component; the proportion of the fast-inactivating component could be decreased by dephosphorylation of a basally phosphorylated Ser-446 on the alpha subunit. To account for our results we suggested a model that assumes a bimodal gating of the alpha(beta) channel. In this study, using single-channel analysis, we confirm this model. Two modes of gating were identified: (1) an inactivating mode characterized by low open probability and single openings early in the voltage step, and (2) a non-inactivating gating mode with bursts of openings. These two modes were non-randomly distributed, with spontaneous shifts between them. Each mode is characterized by a different set of open time constants (tau) and mean open times (t(0)). The non-inactivating mode is similar to the gating mode of a homomultimeric alpha channel. The phosphorylation-deficient alphaS446Abeta channel has the same two gating modes. Furthermore, alkaline phosphatase promoted the transition to the non-inactivating mode. This is the first report of modal behavior of a fast-inactivating K+ channel; furthermore, it substantiates the notion that direct phosphorylation is one mechanism that regulates the equilibrium between the two modes and thereby regulates the extent of macroscopic fast inactivation of a brain K+ channel.
Singer-Lahat
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Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, Israel.
Dascal
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N
Lotan
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I
D000465:Algorithms; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015640:Ion Channel Gating / Q000502:physiology*; D051662:Kv1.1 Potassium Channel; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D014982:Xenopus laevis
D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel; D000469:Alkaline Phosphatase