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

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Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J

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

EMBO J. 1996 Mar 1;15(5):1004-11.

PubMed ID

8605869 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Quinidine	Potassium channel subfamily K member 1	Protein	Humans	Unknown	Inhibitor	Details
Quinidine barbiturate	Potassium channel subfamily K member 1	Protein	Humans	Unknown	Inhibitor	Details

Polypeptides

Name	UniProt ID
Potassium channel subfamily K member 1	O00180	Details