title: Mitochondrial chloride channels: electrophysiological characterization and pH induction of channel pore dilation.
abstract: Physiological and pathological functions of mitochondria are highly dependent on the properties and regulation of mitochondrial ion channels. There is still no clear understanding of the molecular identity, regulation, and properties of anion mitochondrial channels. The inner membrane anion channel (IMAC) was assumed to be equivalent to mitochondrial centum picosiemens (mCS). However, the different properties of IMAC and mCS channels challenges this opinion. In our study, we characterized the single-channel anion selectivity and pH regulation of chloride channels from purified cardiac mitochondria. We observed that channel conductance decreased in the order: Cl⁻ > Br⁻ > I⁻ > chlorate ≈ formate > acetate, and that gluconate did not permeate under control conditions. The selectivity sequence was Br⁻ ≥ chlorate ≥ I⁻ ≥ Cl⁻ ≥ formate ≈ acetate. Measurement of the concentration dependence of chloride conductance revealed altered channel gating kinetics, which was demonstrated by prolonged mean open time value with increasing chloride concentration. The observed mitochondrial chloride channels were in many respects similar to those of mCS, but not those of IMAC. Surprisingly, we observed that acidic pH increased channel conductance and that an increase of pH from 7.4 to 8.5 reduced it. The gluconate current appeared and gradually increased when pH decreased from pH 7.0 to 5.6. Our results indicate that pH regulates the channel pore diameter in such a way that dilation increases with more acidic pH. We assume this newly observed pH-dependent anion channel property may be involved in pH regulation of anion distribution in different mitochondrial compartments.
authors.affiliation: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 83334 Bratislava, Slovak Republic.
authors.forename: Anton
authors.initials: A
authors.lastname: Misak
authors.forename: Marian
authors.initials: M
authors.lastname: Grman
authors.forename: Lubica
authors.initials: L
authors.lastname: Malekova
authors.forename: Marta
authors.initials: M
authors.lastname: Novotova
authors.forename: Jana
authors.initials: J
authors.lastname: Markova
authors.forename: Olga
authors.initials: O
authors.lastname: Krizanova
authors.forename: Karol
authors.initials: K
authors.lastname: Ondrias
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Tomaskova
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000737:chemistry* / Q000378:metabolism*; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005942:Gluconates / Q000378:metabolism; D006016:Glycolates / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D016062:Porosity; D011487:Protein Conformation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D018118:Chloride Channels; D005942:Gluconates; D006016:Glycolates; C015765:MK 473; D008274:Magnesium; C030691:gluconic acid
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