Title : A novel human Cl(-)
channel family related to Drosophila flightless locus
Abstract :
- Large conductance chloride (maxi-Cl(-)) currents have been recorded in some cells, but there is still little information on the molecular nature of the channel underlying this conductance
- We report here that tweety, a gene located in Drosophila flightless, has a structure similar to those of known channels and that human homologues of tweety ( hTTYH1-3 ) are novel maxi-Cl(-) channels
- hTTYH3 mRNA was found to be distributed in excitable tissues
- The whole cell current of hTTYH3 was large enough to be discriminated from the control but emerged only after treatment with ionomycin
- Analysis of pore mutants suggested that positively charged amino acids contributed to anion selectivity
- Like a maxi-Cl(-) channel in situ, the hTTYH3 single channel showed 26-picosiemen linear current voltage, complex kinetics, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid sensitivity, subconductance, and the permeability order of I(-) > Br(-) > Cl(-)
- Similarly, hTTYH2 encoded an ionomycin-induced maxi-Cl(-) channel , but TTYH1 encoded a Ca(2 +)-independent and swelling-activated maxi-Cl(-) channel
- Therefore, the hTTYH family encoded maxi-Cl(-) channels of mammals
- Further studies on the hTTYH family should lead to the elucidation of physiological and pathophysiological roles of novel Cl(-) channel molecules
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