Gating of cx46 gap junction hemichannels by calcium and voltage

被引:0
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作者
Arnold Pfahnl
G. Dahl
机构
[1] Department of Physiology and Biophysics (R-430),
[2] University of Miami School of Medicine,undefined
[3] P.O. Box 016430,undefined
[4] Miami,undefined
[5] Florida 33101,undefined
[6] USA e-mail: gdahl@mednet.med.miami.edu,undefined
[7] Tel.: +1 305 243 5776,undefined
[8] Fax: +1 305 243 5931,undefined
来源
Pflügers Archiv | 1999年 / 437卷
关键词
Key words Lens; Cataract; Connexin; Cysteine; Maleimide; Gap junction; Channel; Gating;
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学科分类号
摘要
 Connexin 46 (cx46), when expressed in Xenopus oocytes, not only forms typical gap junction channels between paired cells but also forms open gap junction hemichannels in the plasma membrane of single cells. The gap junction hemichannels share properties with complete gap junction channels in terms of permeability and gating. Here we characterize the gate that closes hemichannels in response to increased calcium concentration with whole-cell and single-channel records. The channels close within a narrow range of extracellular calcium concentrations (1–2 mM) which includes the calcium concentration prevailing in the primary site of cx46 expression, the lens. The effect of calcium on the channels is determined by voltage. A cysteine mutant of cx46, cx46L35C, was used to determine the localization of the gate. Experimental evidence suggests that position 35 is pore lining. The localization protocol tests the accessibility of position 35 for thiol reagents applied extra- or intracellularly to the channel closed by calcium. Channel closure by calcium excluded the thiol reagent from the outside but not from the inside. Consequently, the gate results in a regional closure of the pore and it is located extracellular to the position 35 of cx46. The present data also suggest that the cx46 gap junction hemichannel may exert a physiological function in the lens. Considering the association of calcium with cataract formation, it is feasible that misregulation of cx46 gap junction hemichannels could be a cause for cataract.
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页码:345 / 353
页数:8
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