Disease relevance of Kcnn4

• The presence of mRNA for SK1, -2, -3, and -4 (intermediate-conductance Ca(2+)-activated K(+) 1 [IK1]) channels was demonstrated by RT-PCR in rodent islets and insulinoma cells [1].
• These drugs have demonstrated efficacy in animal models of cardiac arrhythmias, suggesting that block of IK1 may be a useful antiarrhythmic mechanism [2].
• Transgenic upregulation of IK1 in the mouse heart leads to multiple abnormalities of cardiac excitability [3].
• Similar to other models of cardiac hypertrophy and failure, cardiac myocytes isolated from Galphaq mice show prolonged action potential with reduced transient outward K+ current (Ito) and inward rectifier K+ current (IK1) density compare to wild-type (WT) animals [4].

High impact information on Kcnn4

• The symmetrical action potential (AP)-prolonging and bradycardic effects of these drugs, however, are inconsistent with a sole effect on IK1 [2].
• BACKGROUND: The class III antiarrhythmic agent RP 58866 and its active enantiomer, terikalant, are reported to selectively block the inward rectifier K+ current, IK1 [2].
• Only higher concentrations (> or = 10 mumol/L) of RP 58866 slowed the rate of AP repolarization and decreased resting membrane potential, consistent with an additional but substantially less potent block of IK1 [2].
• SK channels are likely encoded by three genes, Kcnn1-3, whereas IK and most BK channels are most likely products of the Kcnn4 and Slo (Kcnma1) genes, respectively [5].
• The volume regulation of T lymphocytes and erythrocytes was severely impaired in Kcnn4 null mice but was normal in parotid acinar cells [5].

Biological context of Kcnn4

• Up-regulation of the inward rectifier K+ current (IK1) in the mouse heart accelerates and stabilizes rotors [6].

Anatomical context of Kcnn4

• Surprisingly, Kcnn4 channels appear to play no required role in fluid secretion and regulatory volume decrease in the parotid gland [5].
• We conclude that SK1, -2, -3, and IK1 (SK4) are expressed in islet cells and insulin-secreting cells and are able to influence glucose-induced calcium responses, thereby regulating insulin secretion [1].
• These results demonstrate that mIKCa1 is modulator of Paneth cell alpha-defensin secretion and disclose an involvement in mucosal defense of the intestinal epithelium against ingested bacterial pathogens [7].
• Reverse transcriptase-PCR experiments using nested primers amplified mIKCa1 from the lower half of bisected crypts and from single Paneth cells, but not from the upper half of bisected crypts, villus epithelium, or undifferentiated crypt epithelial cells, suggesting a lineage-specific role for mIKCa1 in mouse small bowel epithelium [7].
• The single channel current of intermediate conductance Ca2 +-activated K+ channel (IK channel) was measured in mouse urinary bladder myocytes (MBM), and the molecular basis of the channel was suggested to be the SK4 subtype by RT-PCR [8].

Associations of Kcnn4 with chemical compounds

• Two types of K(+) channels were activated by intracellular Ca(2+) with single-channel conductance values of 22 and 140 pS (in 135 mM external K(+)), consistent with the intermediate and maxi-K classes of Ca(2+)-activated K(+) channels, typified by the mIK1 (Kcnn4) and mSlo (Kcnma1) genes, respectively [9].
• Of great interest is the effect of melatonin upon the expression of a large number of genes related to calcium exchange, such as Cul5, Dcamkl1 and Kcnn4; a significant effect of melatonin on the expression of some oncogenesis-related genes was also detected [10].

Regulatory relationships of Kcnn4

• These data suggest that IK1 channels inhibit maxi-K channel activity via a direct, membrane-delimited interaction between the channel proteins [11].

Other interactions of Kcnn4

• Among them, a group of ion channels show specific regulation in CB: the potassium channels Kir6.1 and Kcnn4 are up-regulated, while the modulatory subunit Kcnab1 is down-regulated by low PO2 levels [12].

Analytical, diagnostic and therapeutic context of Kcnn4

• The properties of the inward-rectifying potassium current (IK1) were studied in the single myocytes isolated from adult mouse ventricles by the whole-cell patch-clamp technique for the first time [13].

References