Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation

Abstract

Modulation of neuronal excitability by regulation of K+ channels potentially plays a part in short-term memory but has not yet been studied at the molecular level. Regulation of K+ channels by protein phosphorylation and oxygen has been described for various tissues and cell types; regulation of fast-inactivating K+ channels mediating IK(A) currents has not yet been described. Functional expression of cloned mammalian K+ channels has provided a tool for studying their regulation at the molecular level. We report here that fast-inactivating K+ currents mediated by cloned K+ channel subunits derived from mammalian brain expressed in Xenopus oocytes are regulated by the reducing agent glutathione. This type of regulation may have a role in vivo to link metabolism to excitability and to regulate excitability in specific membrane areas of mammalian neurons.

Molecular and functional characterization of a rat brain Kvβ3 potassium channel subunit

“…The time course of inactivation in oxidizing environments corresponds to the control where Kvl.4AI-110 was injected only (see [6]). A similar regulation of inactivation by oxidation was found for Kvl.4 and Kv3.4 channels [8] as well as for inactivation induced by the Kj~I, 1 subunit [6]. In those studies, the regulation could be attributed to a cysteine residue in the N-terminal inactivating structure; the mutations C 13S in Kv1.…”

A structural determinant of differential sensitivity of cloned inward rectifier K+ channels to intracellular spermine

“…While inward-going currents increased very quickly, the outward currents increased slowly, within about 30 s in all experiments (n = 18). Similarly, after exposing the patch again to the cytoplasm of the oocyte by cramming through the cell membrane [26] currents were again blocked, and outward currents slowly reappeared when the patch was re-exposed to the K-Int,,, solution ( Fig. 1A; n = 5).…”

Heme impairs the ball-and-chain inactivation of potassium channels

“…For example, molecular processes affecting the speed and degree of N-type inactivation in Kv1.4 (KCNA4) channels include redox regulation of a cysteine residue in the N-terminal ball structure (C13) (10), protonation of histidine at position 16 (11), interaction with membrane lipids (12), and Ca 2+ -dependent phosphorylation (13). Furthermore, low-molecular-weight compounds affecting N-type inactivation (N-type disinactivators) have been discussed as potential drugs regulating cellular excitability (14).…”