TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure.

Abstract

A new human weakly inward rectifying K+ channel, TWIK‐1, has been isolated. This channel is 336 amino acids long and has four transmembrane domains. Unlike other mammalian K+ channels, it contains two pore‐forming regions called P domains. Genes encoding structural homologues are present in the genome of Caenorhabditis elegans. TWIK‐1 currents expressed in Xenopus oocytes are time‐independent and present a nearly linear I‐V relationship that saturated for depolarizations positive to O mV in the presence of internal Mg2+. This inward rectification is abolished in the absence of internal Mg2+. TWIK‐1 has a unitary conductance of 34 pS and a kinetic behaviour that is dependent on the membrane potential. In the presence of internal Mg2+, the mean open times are 0.3 and 1.9 ms at −80 and +80 mV, respectively. The channel activity is up‐regulated by activation of protein kinase C and down‐regulated by internal acidification. Both types of regulation are indirect. TWIK‐1 channel activity is blocked by Ba2+(IC50=100 microM), quinine (IC50=50 microM) and quinidine (IC50=95 microM). This channel is of particular interest because its mRNA is widely distributed in human tissues, and is particularly abundant in brain and heart. TWIK‐1 channels are probably involved in the control of background K+ membrane conductances.

Identification and cloning of TWIK‐originated similarity sequence (TOSS): a novel human 2‐pore K+ channel principal subunit

“…We were unable to detect currents above background in oocytes expressing hTOSS. Despite the initial report that TWIK may express weakly inwardly rectifying currents [3], we were unable to demonstrate a signi¢cant current in oocytes injected with TWIK-1 cRNA. This ¢nding is consistent with the ¢ndings of others [20] who have also been unable to demonstrate TWIK-1 currents in Xenopus oocytes.…”

“…They are unique in exhibiting a novel topology of four transmembrane domains and two P-domains within a single continuous polypeptide (K2P family). These novel channel-forming subunits include TWIK (tandem of P-domains in a weak inward rectifying K channel) [3], TREK (TWIK-1-related K channel) [4], TASK (TWIK-1-related acid-sensitive K channel) [5] and TRAAK (TWIK-related arachidonic acid-stimulated K channel) [6]. Except for the P-domains, there is a low level of amino acid similarity between these subunits (30^34%).…”

High Activity K+ Channels in Rat Hippocampal Neurones Maintained in Culture

“…IRK1) K¤ inward rectifiers have single channel conductance of 21-22 pS (Matsuda, 1988;Kubo et al 1993). TWIK channels can have a conductance of 19 pS, but only at + 80 mV, and in the presence of Mg¥ (Lesage et al 1996). The conductance of this channel is 34 pS at −80 mV.…”

“…Equally, whether other channels contribute to the resting membrane conductance of central neurones has yet to be determined. For example, the inwardly rectifying tandem of P domains (TWIK) channel may help set the resting conductance (Lesage et al 1996). Indeed the nature of the ion channels which determine the resting membrane potential of many neurones including the squid giant axon remains to be defined (Chang, 1986(Chang, , 1988.…”

Canaux K2Pneuronaux : aspects moléculaires et fonctionnels

“…Les sous-unités à deux domaines P (notés P1 et P2) ont été identifiées à partir de recherches dans les banques de données issues du séquençage systématique des génomes. Le premier membre cloné de cette classe, appelé TWIK1 (tandem of P domains in a weak inwardlyrectifying K + channel), possède quatre segments transmembranaires (M1 à M4) [5]. Depuis, 14 sous-unités K 2P ont été identifiées chez les mammifères et classées en six sous-groupes selon leurs homologies structurales et fonctionnelles [6,7] ( Figure 2).…”