絞り込み

16738

広告

EAVK "segment c" sequence confers Ca(2+)-dependent changes to the kinetics of full length human Ano1.

著者 Strege PR , Gibbons SJ , Mazzone A , Bernard CE , Beyder A , Farrugia G
Am J Physiol Gastrointest Liver Physiol.2017 Mar 23 ; ():ajpgi.00429.2016.
この記事をPubMed上で見るPubMedで表示
この記事をGoogle翻訳上で見る Google翻訳で開く

スターを付ける スターを付ける     (8view , 0users)

Full Text Sources

Miscellaneous

Anoctamin1 (Ano1, TMEM16A) is a calcium-activated chloride channel specifically expressed in interstitial cells of Cajal (ICC) of the gastrointestinal (GI) tract muscularis propria. Ano1 is necessary for normal electrical slow waves and ICC proliferation. The full length human Ano1 sequence includes an additional exon, exon "0," at the N-terminus. Ano1 with exon "0" (Ano1(0)) had a lower EC50 for intracellular calcium ([Ca(2+)]i) and faster chloride current (ICl) kinetics. The Ano1 alternative splice variant with segment "c" encoding exon 13 expresses on the first intracellular loop four additional amino acid residues, EAVK, which alter ICl at low [Ca(2+)]i Exon 13 is expressed in 75-100% of Ano1 transcripts in most human tissues but only 25% in human stomach. Our aim was to determine the effect of EAVK deletion on Ano1(0) ICl parameters. By voltage-clamp electrophysiology, we examined ICl in HEK293 cells transiently expressing Ano1(0) with or without the EAVK sequence (Ano1(0)ΔEAVK). The EC50 values of activating and deactivating ICl for [Ca(2+)]i was 438±7 and 493±9 nM for Ano1(0) but higher for Ano1(0)ΔEAVK at 746±47 and 761±26 nM, respectively. Meanwhile, the EC50 values for the ratio of instantaneous to steady-state ICl were not different between variants. Congruently, the time constant of activation was slower for Ano1(0)ΔEAVK than Ano1(0) currents at intermediate [Ca(2+)]i These results suggest that EAVK decreases the calcium sensitivity of Ano1(0) current activation and deactivation by slowing activation kinetics. Differential expression of EAVK in human stomach may function as a switch to increase sensitivity to [Ca(2+)]i via faster gating of Ano1.
PMID: 28336549 [PubMed - as supplied by publisher]
印刷用ページを開く Endnote用テキストダウンロード