The corticosteroid hormone induced factor: a new modulator of KCNQ1 channels?
The corticosteroid hormone induced factor (CHIF) is a member of the one-transmembrane segment protein family named FXYD, which also counts phospholemman and the Na,K-pump gamma-subunit. Originally it was suggested that CHIF could induce the expression of the I(Ks) current when expressed in Xenopus laevis oocytes, but recently CHIF has attracted attention as a modulatory subunit of the Na,K-pump. In renal and intestinal epithelia, the expression of CHIF is dramatically up-regulated in response to aldosterone stimulation, and regulation of epithelial ion channels by CHIF is an attractive hypothesis. To study a potential regulatory effect of the CHIF subunit on KCNQ1 channels, co-expression experiments were performed in Xenopus laevis oocytes and mammalian CHO-K1 cells. Electrophysiological characterization was obtained by two-electrode voltage-clamp and patch-clamp, respectively. In both expression systems, we find that CHIF drastically modulates the KCNQ1 current; in the presence of CHIF, the KCNQ1 channels open at all membrane potentials. Thereby, CHIF is the first accessory subunit shown to be capable of modulating both the Na,K-pump and an ion channel. To find a possible physiological function of the constitutively open KCNQ1/CHIF complex, the precise localization of KCNQ1 and CHIF in distal colon and kidney from control and salt-depleted rats was determined by confocal microscopy. However, in these tissues, we did not detect an obvious overlap in expression between KCNQ1 and CHIF. In conclusion, the hormone-regulated subunit CHIF modulates the voltage sensitivity of the KCNQ channels, but so far evidence for an actual co-localization of CHIF and KCNQ1 channels in native tissue is lacking.
Department of Medical Physiology and Danish Arrhythmia Research Centre, The Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
Thomas
T
Jespersen
Morten
M
Grunnet
Hanne B
HB
Rasmussen
Nils B
NB
Jørgensen
Henrik S
HS
Jensen
Kamilla
K
Angelo
Søren-Peter
SP
Olesen
Dan A
DA
Klaerke
D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D016466:CHO Cells; D003106:Colon / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D051657:KCNQ1 Potassium Channel / Q000187:drug effects* / Q000502:physiology*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis / Q000502:physiology*; D018613:Microscopy, Confocal; D009865:Oocytes; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D051381:Rats; D014982:Xenopus laevis
C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D051657:KCNQ1 Potassium Channel; C484268:Kcne1 protein, rat; D008565:Membrane Proteins; D024642:Potassium Channels, Voltage-Gated; C422209:corticosteroid hormone-induced factor; D000450:Aldosterone