Disease relevance of CLCA4

• CaCC is preserved and seems to be up-regulated in the airways of cystic fibrosis (CF) patients [1].
• Co-activation of hKvLQT1 improves CaCC-mediated Cl- secretion in native CF airway epithelia, and may have a therapeutic effect in the treatment of CF lung disease [1].
• However, the expression levels of all the CaCC genes were significantly decreased in nasal polyp [2].

High impact information on CLCA4

• ASL volume is maintained by the predominantly ciliated epithelium via coordinated regulation of (a) absorption, by the epithelial Na(+) channel, and (b) secretion, by the Ca(2+) -activated Cl() channel (CaCC) and CFTR [3].
• At the apical membrane, the secretion of moderate concentrations of HCO3- can be explained by the parallel activity of a Cl-/HCO3- exchanger and a Cl- conductance, either the cystic fibrosis transmembrane conductance regulator (CFTR) or a Ca2+-activated Cl- channel (CaCC) [4].
• Expression of hCLCA1 and hCLCA4 in human rectal mucosa was proven by microarray analysis [5].
• Transmission disequilibrium and the significance of the association decreased within the locus from hCLCA2 towards hCLCA4 [5].
• CaCC-dependent ion transport was inhibited by the chromanol 293B, an inhibitor of cAMP-activated hKvLQT1 K+ channels, and by clotrimazole, an inhibitor of Ca2+-activated hSK4 K+ channels [1].

Biological context of CLCA4

• In the present study, we examined the role of basolateral K+ channels in CaCC-mediated Cl- secretion in native nasal tissues from normal individuals and CF patients by measuring ion transport in perfused micro Ussing chambers [1].
• Treatment with these CaCC inhibitors (NA, FA, NPPB, and DIDS) markedly prevented the CsA-induced apoptosis [6].

Anatomical context of CLCA4

• Activation of the cAMP pathway further increased CaCC-mediated secretion in CF but not in normal nasal mucosa [1].
• Using the voltage-clamp technique, the present study investigated the potential role of 14-3-3 in modulating the Ca(2+)-activated Cl(-) channel (CaCC) endogenously expressed in Xenopus oocytes [7].
• Expression of a CaCC in exocrine pancreas has been confirmed by RT-PCR analysis, and by immunoblotting and immunogold labeling of ZG membranes [8].
• RESULTS: mRNAs for kNBC, KCC1 and -4 and all the CaCC families (CaCC1, -2 and -3) are expressed in human turbinate mucosa and nasal polyp [2].

Associations of CLCA4 with chemical compounds

• Taken together these findings demonstrate the existence of several CaCC-like genes in humans, some of which display distinct tissue specificity patterns within the CaCC subfamily of chloride channels [9].
• The K+ channel opener 1-ethyl-2-benzimidazolinone further increased CaCC-mediated Cl- secretion in normal and CF tissues [1].

References