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Zinc permeates mouse muscle ACh receptor channels expressed in BOSC 23 cells and affects channel function
Author(s) -
Ragozzino Davide,
Giovannelli Aldo,
Degasperi Valentina,
Eusebi Fabrizio,
Grassi Francesca
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00083.x
Subject(s) - acetylcholine receptor , biophysics , patch clamp , chemistry , nicotinic agonist , receptor , ion channel , acetylcholine , membrane potential , biochemistry , biology , endocrinology
1 The influx of Zn 2+ through the channels of fetal and adult mouse muscle nicotinic acetylcholine receptors (γ‐ and ε‐AChRs) and its effects on receptor function were studied in transiently transfected human BOSC 23 cells, by combining patch‐clamp recordings with digital fluorescence microscopy. 2 ACh‐induced whole‐cell currents were reversibly reduced by external ZnCl 2 , with half‐maximal inhibitory concentrations of 3 and 1 mM for γ‐ and ε‐AChRs, respectively. 3 Both γ‐ and ε‐AChR channels were permeable to Zn 2+ , as shown by fluorescence measurements using Zn 2+ ‐sensitive dyes. The fractional current carried by Zn 2+ ( P f,Zn ; 0.5 mM Zn 2+ in Ca 2+ ‐ and Mg 2+ ‐free medium) through γ‐ and ε‐AChR channels was 1.7 and 4 %, respectively. 4 Pf,Zn increased with the concentration of ZnCl 2 , but was little affected by physiological concentrations of Ca 2+ and Mg 2+ in the external medium. 5 The conductance of ACh‐evoked unitary events, measured by cell‐attached or outside‐out recordings, decreased when the patched membrane was exposed to ZnCl 2 (1 or 3 mM). Simultaneous application of ACh and Zn 2+ to the extra‐patch membrane lengthened channel open duration (τ op ) by 50%. No obvious increment of τ op was observed following exposure of inside‐out patches to Zn 2+ . 6 The possible physiological relevance of zinc‐induced modulation of AChR channels is discussed.