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This Article Full Text Full Text (PDF) All Versions of this Article: 91/1/141    most recent expphysiol.2005.031773v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Suzuki, M. Search for Related Content PubMed PubMed Citation Articles by Suzuki, M. Related Collections Symposia Papers Genomic Physiology

¹ Department of Pharmacology, Division of Molecular Pharmacology, Jichi Medical School 3311-1, Yakushiji, Minamikawachi, Tochigi, 329-0498, Japan

Abstract

Calcium-activated chloride currents (I_Cl(Ca)) can be recorded in almost all cells, but the molecular identity of the channels underlying this Cl^– conductance is still incompletely understood. Here, I report that tweety, a gene located in Drosophila flightless, possesses five or six transmembrane segments, and that a human homologue of tweety (hTTYH3) is a novel large-conductance Ca²⁺-activated Cl^– channel, while the related gene, hTTYH1, is a swelling-activated Cl^– current. hTTYH3 is expressed in excitable tissues, including the heart, brain and skeletal muscle, whereas hTTYH1 is expressed mainly in the brain. Expression of hTTYH3 in CHO cells generated a unique Cl^– current activated by an increase in the intracellular Ca²⁺ concentration. The hTTYH3-induced Cl^– current had a linear current–voltage (I–V) relationship, a large single-channel conductance (260 pS) and the anion permeability sequence I^– > Br^– > Cl^–. Like native Ca²⁺-activated Cl^– channels, the hTTYH3 channel showed complex gating kinetics and voltage-dependent inactivation, and was dependent on micromolar intracellular Ca²⁺ concentration. Expression in CHO cells of an hTTYH1 splice variant that lacks the C-terminal glutamate-rich domain of hTTYH1 (hTTYH1sv) generated a swelling-activated Cl^– current. I conclude that investigation of the tweety family will provide important information about large-conductance Cl^– channel molecules.

(Received 23 August 2005; accepted after revision 11 October 2005; first published online 11 October 2005)
Corresponding author M. Suzuki: Department of Pharmacology, Division of Molecular Pharmacology, Jichi Medical School 3311-1, Yakushiji, Minamikawachi, Tochigi, 329-0498, Japan. Email: macsuz{at}jichi.ac.jp

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