Cloning of a human cDNA expressing a high voltage‐activating. Tea‐sensitive, type‐a K⁺ channel which maps to chromosome 1 band p21

Abstract

Over ten different mammalian genes related to the Drosophila Shaker gene (the Sh gene family) have been identified recently. These genes encode subunits of voltage-dependent K+ channels. The family consists of four subfamilies: ShI genes are homologues of Shaker; ShII, ShIII, and ShIV are homologues of three other Shaker-like genes in Drosophila, Shab, Shaw, and Shal, respectively. We report here the cloning of a human K+ channel ShIII cDNA (HKShIIIC) obtained from a brain stem cDNA library. HKShIIIC transcripts express an atypical voltage-dependent transient (A-type) K+ current in Xenopus oocytes. This current is activated by large membrane depolarizations and is extremely sensitive to the K+ channel blocker TEA unlike most A-type currents. The gene encoding HKShIIIC maps to chromosome 1p21.

Kv3.4 channel function and dysfunction in nociceptors

“…7,8,[12][13][14]17,18 Moreover, Kv3.4 siRNA nearly ablates the high voltageactivated K C current in small-diameter DRG neurons. 7 Although fast-inactivating slowing of macroscopic inactivation in DRG nociceptors under normal conditions (Fig.…”

“…8 The Kv3.4 N-terminal inactivation domain (NTID) underlies fast inactivation of the corresponding currents. [12][13][14] Early reports showed modulation of fast Kv3.4 channel inactivation by oxidation, phosphorylation and PIP2 in heterologous expression systems. [15][16][17][18] Demonstrating that inactivation modulation also occurs in neurons, we showed that PKC activation dramatically slows inactivation of the native Kv3.4 channel expressed in DRG nociceptors.…”

Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate

“…This channel is encoded by hKv3.4, a member of the Shaw subfamily of K + channel genes related to Shaker (Wei et al, 1990;Rudy et al, 1991;Schroter et al, 1991). Comparing the configuration of basic residues at the N-terminus of several inactivating K + channels, we were struck by their close correspondence with unique serine residues in hKv3.4.…”

Inactivation of the cloned potassium channel mouse Kv1.1 by the human Kv3.4 ‘ball’ peptide and its chemical modification.

“…The hKv3.4 peptide was based on part of the N-terminal of the deduced sequence of the rapidly inactivating hKv3.4 channel cloned from a human brainstem cDNA library (Rudy, Sen, Vega-Saenz de Miera, Lau, Ried & Ward, 1991) and the rat homologue Raw3 similarly cloned from a rat cortex library (Schrbter, Ruppersberg, Wunder, Rettig, Stocker & Pongs, 1991 Comparison of the actions of hKv3.4 and ShB peptides on mKvl.1…”