Disease relevance of KCNK1

• TWIK-1 was also detected in the cytoplasm of the large neurons of vestibular ganglion and their fibers [1].
• Finally, chronic atrial fibrillation was associated with reduced atrial expression of the potassium channel TWIK-1, suggesting potential contribution of the corresponding current to electrical remodeling [2].

Psychiatry related information on KCNK1

• Nucleotide sequence analysis of the two cDNAs identified known genes not previously associated with the pathogenesis of AIDS dementia, including the neurotrophin receptor tyrosine kinase receptor B (TrkB) and the potassium channel human open rectifyer K+ channel (ORK) homologous open reading frame (HOHO1) [3].

High impact information on KCNK1

• TWIK-1 channel activity is blocked by Ba2+(IC50=100 microM), quinine (IC50=50 microM) and quinidine (IC50=95 microM) [4].
• 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+ [4].
• TWIK-1 has a unitary conductance of 34 pS and a kinetic behaviour that is dependent on the membrane potential [4].
• Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge [5].
• CONCLUSIONS: mRNAs for all 4 IRKs are detected in human atrium and ventricle, but the mRNA copy number of a low-conductance subunit (HIR) is larger in atrium and the copy number of a weakly rectifying subunit (TWIK-1) is larger in ventricle [6].

Biological context of KCNK1

• We conclude that KCNK1 is a unique, double-pore, mammalian K channel, distantly related to the yeast channel TOK1, that is expressed in distal tubule and is a candidate to participate in renal K homeostasis [7].
• Assignment of the human weak inward rectifier K+ channel TWIK-1 gene to chromosome 1q42-q43 [8].
• The major focus of the study, however, was to systematically examine gene expression levels of the KCNK family of K(+)-selective leak channels [9].
• DPK expressing dominant-negative (dn)Rac1 underwent massive apoptosis upon TCR stimulation and resulted in defective differentiation of CD4-SP cells [10].
• Because we can strictly synthesize various DPK derivatives, which have several types of branch units, terminal cationic groups, and so on, they are expected to be a good object of study regarding the basic information on the detailed mechanism of gene transfection into cells [11].

Anatomical context of KCNK1

• Toward this goal, we built upon previous studies of voltage-gated K(+)-selective ion channels (Kv), and expanded our analysis to K(+)-selective leak channels (KCNK), which can play a major role in setting the basic firing characteristics of spiral ganglion neurons [9].
• Expression of TWIK-related acid sensitive K+ channels in capsaicin sensitive and insensitive cells of rat dorsal root ganglia [12].
• Cellular localization of TWIK-1, a two-pore-domain potassium channel in the rodent inner ear [1].
• Reverse transcription-polymerase chain reaction showed that TWIK-1 mRNA is present in the vestibular end organs, vestibular ganglion and cochlea [1].
• Immunocytochemical experiments using confocal microscopy showed that TWIK-1 is specifically localized in 'non-sensory' cells of the inner ear, in the dark cells of the vestibule and in the strial marginal cells of the cochlea [1].

Associations of KCNK1 with chemical compounds

• Cloning and localization of a double-pore K channel, KCNK1: exclusive expression in distal nephron segments [7].
• Low-density lipoprotein was derived from carbamyl (carbamyl-LDL) by incubating LDL in potassium cyanate (KCNO) [13].
• Modification of amino acid residues by KCNO treatment completely destroys binding capacity, indicating crucial involvement of lysine residues in binding of beta 2-glycoprotein I to cardiolipin [14].
• The spectra of the oxygenated forms change little upon addition of KCNO, which is known to carbamoylate the NH2 terminals of the individual chains (Cerami and Manning, 1971) [15].
• Some loss of 18O also occurred during an enzymic synthesis with KCNO, [18O]Pi, carbamate kinase, and pyruvate kinase [16].

Regulatory relationships of KCNK1

• Human TWIK-2 expressed heterologously in Xenopus oocytes is a non-inactivating weak inward rectifier with channel properties similar to TWIK-1 [17].

Other interactions of KCNK1

• Several sub-families of the two pore domain potassium channel family have been described, including the weakly inward rectifying K+ channel (TWIK), the acid-sensitive K+ channel (TASK), the TWIK-related K+ channel (TREK) and the TWIK-related arachidonic acid stimulated K+ channel (TRAAK) [18].
• Pharmacologically, TWIK-2 channels are distinct from TWIK-1 channels in their response to quinidine, quinine, and barium [17].

Analytical, diagnostic and therapeutic context of KCNK1

• Primary sequence analysis of TWIK-2 shows that it is most closely related to TWIK-1, especially in the pore-forming domains [17].
• The major allergen of C. arizonica (Cup a 1), purified by anion exchange chromatography, was checked by immunoblotting experiments before chemical modification, in parallel with a C. arizonica extract, with potassium cyanate (KCNO) to obtain a monomeric allergoid [19].
• Par j I allergen was then modified by reaction with potassium cyanate (KCNO), and compared with the native allergen to evaluate its allergenic potency (RAST-inhibition) and molecular weight (SDS-PAGE) [20].
• Using RT-PCR and a semiquantitative method to detect relative differences in mRNA expression, we examined uterine smooth muscle from both pregnant and non-pregnant women for the expression of members of weak inwardly rectifying 2-pore potassium channel family (TWIK), TREK and TRAAK [21].
• RT-PCR revealed expression of the acid-sensitive, twin P domain K+ channel TASK but not of TWIK, TREK, or the known hypoxia-sensitive Kv2.1, which was confirmed by sequencing and further PCR with primers to the coding region of TASK [22].

References