Disease relevance of Kcna1

• Linkage studies in four such families suggested localization of an EA/myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p [1].
• Using patch-clamp techniques, this study investigated the effect of hypoxia on recombinant Kv1 channels previously identified in pulmonary artery (Kv1.1, Kv1.2, and Kv1.5) and Kv3.1b, which has similar kinetic and pharmacological properties to native oxygen-sensitive currents [2].
• Episodic ataxia type-1 mutations in the Kv1.1 potassium channel display distinct folding and intracellular trafficking properties [3].
• These results suggest that as in many neurodegenerative disorders, intracellular aggregation of misfolded Kv1.1-containing channels may contribute to the pathophysiology of EA-1 [3].
• Herein, reactive astrocytes from a rat cerebellar lesion were shown to contain Kv1.1, -1.2, -1.3, -1.4, and -1.6 alpha plus beta1.1 subunits, as well as an unusual beta2.1 constituent; the latter was also found in a glioblastoma C6 cell line, together with Kv1.1, -1.3, and -1.6 and beta1.1 subunits [4].

Psychiatry related information on Kcna1

• Furthermore, while no behavioral disturbances during spatial acquisition in the Morris water maze were observed with overexpression of either channel, animals overexpressing SK2, but not Kv1.1, exhibited a memory deficit post-training [5].
• Finally, Kv1.1 mRNA levels in the hippocampus were positively correlated with odor-reward association learning in rats that were beginning to discriminate between odors [6].

High impact information on Kcna1

• We report here that heteromultimeric K+ channels composed of two different RCK proteins (RCK1 and RCK4) assemble after cotransfection of HeLa cells with the corresponding cDNAs and after coinjection of the corresponding cRNAs into Xenopus oocytes [7].
• The heteromultimeric RCK1, 4 channel mediates a transient potassium outward current, similar to the RCK4 channel but inactivates more slowly, has a larger conductance and is more sensitive to block by dendrotoxin and tetraethylammonium chloride [7].
• Second, coimmunoprecipitation experiments of cotranslated Kv1.1 and Kv1.5 truncated polypeptides show that the S1 segment is essential for coimmunoprecipitation [8].
• We have compared the distribution of mRNAs of three K+ channel genes, Kv1.1, Kv1.2, and Kv4.2 in rat brain, and examined activity-dependent changes following treatment with the convulsant drug pentylenetetrazole [9].
• The two most abundant RCK potassium channel mRNAs (RCK1 and RCK5) are predominantly expressed in the adult nervous system [10].

Biological context of Kcna1

• Glycosylation affects rat Kv1.1 potassium channel gating by a combined surface potential and cooperative subunit interaction mechanism [11].
• Kv1.1 and Kv1.4 potassium channels are plasma membrane glycoproteins involved in action potential repolarization [12].
• Transient transfection experiments of COS-7 cells revealed that the S1 mutants directed the synthesis of Kv1.1 polypeptides [13].
• Heterologous coexpression of Kv1.1 and Kv1.2 subunits in COS-1 cells leads to the formation of a complex that combines the pharmacological profile of both parent subunits, reconstituting the native MgTX receptor phenotype [14].
• We found that EA-1 missense mutations generate mutant Kv1.1 subunits with folding and intracellular trafficking properties indistinguishable from wild-type Kv1 [3].

Anatomical context of Kcna1

• Furthermore, the Kv1.3 and Kv1.1 proteins appear to be expressed in the apical membrane of the epithelial cells in immunocytochemical studies [15].
• In conclusion, Kv1.1 and Kv1.3 channels make a significant contribution to K+ efflux at the apical membrane of the choroid plexus [15].
• Whole cell K+ currents were significantly reduced by 10 nM dendrotoxin-K and 1 nM margatoxin, which are specific inhibitors of Kv1.1 and Kv1.3 channels, respectively [15].
• Image analysis demonstrated the specific increase in Kv1.1 immunoreactivity in aged cochlear nucleus neurons although the mean density of the entire selection was significantly decreased [16].
• Kv1.1 immunoreactivity was increased in the octopus cell bodies, while the staining intensity was significantly decreased in the neuropil [16].

Associations of Kcna1 with chemical compounds

• However, in both chick and rat hepatocytes in culture, MeIQ decreased the amount of 3-methylcholanthrene-induced ethoxyresorufin deethylase activity, which is catalyzed by cytochrome P450 IA [17].
• The data suggest that sialic acid addition modifies Kv1.1 channel function, possibly by influencing the local electric field detected by its voltage sensor, but that these carbohydrates are not required for cell surface expression [18].
• Kv1.1 potassium (K+) channels contain significant amounts of negatively charged sialic acids [18].
• Here we report that the mutation of these residues in Kv1.1 to leucine, proline, or arginine abolished the expression of outward potassium currents in Xenopus oocytes [13].
• Phenol (2.5 mM) caused a 43 +/- 5 mV depolarizing shift in the RCK1 half-activation voltage (Vg) but only a 10 +/- 3% decrease in the peak conductance at 80 mV [19].

Other interactions of Kcna1

• 1. The potassium channel beta-subunit from rat brain, Kv beta 1.1, is known to induce inactivation of the delayed rectifier channel Kv1.1 and Kv1.4 delta 1-110 [20].
• DISCUSSION: This study may provide useful data to compare age-related changes in Kv1.1 and Kv3.1 with known physiological properties of auditory neurons [16].
• Exposure to chronic hypoxia decreased mRNA and protein levels of Kv1.1, Kv1.5, Kv1.6, Kv2.1, and Kv4.3 alpha-subunits in dPAs but did not alter gene or protein expression of these channels in aorta [21].
• Here we examined the association and colocalization of two mammalian beta-subunits, Kvbeta1 and Kvbeta2, with the K+ channel alpha-subunits Kv1.1, Kv1.2, Kv1.4, Kv1.6, and Kv2.1 in adult rat brain [22].
• An immunocytochemical survey of voltage-gated K(+) channel subunits characteristic of adult tissue demonstrated the presence in vitro of Kv1.1, Kv1.4, Kv4.2, Kv4.3, and Kvbeta1.1, which have been associated with the rapidly inactivating currents [23].

Analytical, diagnostic and therapeutic context of Kcna1

• Western blot analysis indicated the presence of Kv1.1 and Kv1.3 proteins in the choroid plexus [15].
• The K+ channel alpha-subunits Kv1.1 and Kv1.2 and the cytoplasmic beta-subunit Kvbeta2 were detected by immunofluorescence microscopy and found to be colocalized at juxtaparanodes in normal adult rat sciatic nerve [24].
• Immunoprecipitation experiments revealed that all 125I-MgTX receptors contain at least one Kv1.2 subunit and that 83% of these receptors are heterotetramers of Kv1.1 and Kv1.2 subunits [14].
• Voltage-gated potassium channels, Kv1.1, Kv1.2 and Kv1.6, were identified as PCR products from mRNA prepared from nodose ganglia [25].
• Confocal immunohistochemistry showed a markedly dispersed labelling of Kv1.1 and Kv1.2 along the injured axons, in contrast to the tight localization of these channels to the juxtaparanodes of noninjured axons [26].

References