Disease relevance of Kcna6

• This suggests that impaired Kv2 channel activity may contribute to arterial dysfunction during hypertension [1].
• A chimeric protein containing the hemagglutinin protein from influenza virus and the region of Kv2.1 that differentiates the two truncation mutants (amino acids 536-666) was also expressed in MDCK cells, where it was found in high density clusters similar to those observed for Kv2 [2].
• In cultured rat hippocampal neurons, chemical ischemia (CI) elicited a similar dephosphorylation and translocation of Kv2 [3].

High impact information on Kcna6

• The Kv2 mRNA is expressed only in brain, whereas the Kv1 and Kv3 transcripts are found in several other tissues as well [4].
• RCK2 mRNA was detected predominantly in midbrain areas and brainstem [5].
• Here we report the cloning of a novel gene encoding a Kv channel binding protein (KChAP, for K+ channel-associated protein), which modulates the expression of Kv2 channels in heterologous expression system assays [6].
• This study establishes that Kv2 and 1 channel homologs mediate the majority of repolarizing delayed rectifier current in rat beta-cells and that antagonism of Kv2.1 may prove to be a novel glucose-dependent therapeutic treatment for type 2 diabetes [7].
• Phosphoamino acid analysis of Kv2.1 expressed in transfected cells and labeled in vivo with 32P shows that phosphorylation was restricted to serine residues and that a truncation mutant, DeltaC318, which lacks the last 318 amino acids in the cytoplasmic carboxyl terminus, was phosphorylated to a much lesser degree than was wild-type Kv2 [8].

Chemical compound and disease context of Kcna6

• We also found that during angiotensin II-induced hypertension, Kv2 channel function was reduced in isolated myocytes and in intact arteries [1].

Biological context of Kcna6

• In addition, our analysis indicates that a substantial component (approximately 50%) of the voltage dependencies and kinetics of Kv currents in voltage-clamped cerebral arterial myocytes is consistent with Kv2 channels [1].
• The deduced amino acid sequence is 816 residues, and shares a 56-59% sequence identity with Kv2.1 and Kv2.2, the other members of the vertebrate Kv2 subfamily of voltage-gated K(+) channels [9].
• Neither of the two protocols affected gene expression of the ion channel-associated proteins Kir6.2, sulfonylurea receptor 1, voltage-dependent calcium channel-alpha1, or Kv2 [10].
• Finally, Chinese hamster ovary cells, which do not express endogenous voltage-gated K+ channels, became substantially more sensitive to apoptosis after transient expression of wild-type Kv2 [11].

Anatomical context of Kcna6

• A novel member of the RCK family of rat brain K+ channels, called RCK2, has been sequenced and expressed in Xenopus oocytes [12].
• In this study, we tested the hypothesis Kv2 channels may also significantly regulate tone of rat cerebral arteries [1].
• On the basis of these novel observations, we propose a new model of Kv channel function in arterial smooth muscle in which Kv2 channels (in combination with Kv1 channels) contribute to membrane hyperpolarization and thus oppose constriction [1].
• Taken together, results provide evidence for the expression of Kv2 sequences in the X. laevis inner ear and brain [13].

Associations of Kcna6 with chemical compounds

• We report here that the cytoplasmic NH2-terminal domains of Kv1, Kv2, Kv3, and Kv4 subfamilies each associate to form homomultimers [14].
• Adenovirus-mediated expression of a C-terminal truncated Kv2.1 subunit, specifically eliminating Kv2 family currents, reduced delayed rectifier currents in these cells by 60-70% and enhanced glucose-stimulated insulin secretion from rat islets by 60% [7].

Analytical, diagnostic and therapeutic context of Kcna6

• Kv2 channels oppose myogenic constriction of rat cerebral arteries [1].

References