title: Modulation of intracellular chloride channels by ATP and Mg2+.
abstract: We report the effects of ATP and Mg2+ on the activity of intracellular chloride channels. Mitochondrial and lysosomal membrane vesicles isolated from rat hearts were incorporated into bilayer lipid membranes, and single chloride channel currents were measured. The observed chloride channels (n=112) possessed a wide variation in single channel parameters and sensitivities to ATP. ATP (0.5-2 mmol/l) modulated and/or inhibited the chloride channel activities (n=38/112) in a concentration-dependent manner. The inhibition effect was irreversible (n=5/93) or reversible (n=15/93). The non-hydrolysable ATP analogue AMP-PNP had a similar inhibition effect as ATP, indicating that phosphorylation did not play a role in the ATP inhibition effect. ATP modulated the gating properties of the channels (n=6/93), decreased the channels' open dwell times and increased the gating transition rates. ATP (0.5-2 mmol/l) without the presence of Mg2+ decreased the chloride channel current (n=12/14), whereas Mg2+ significantly reversed the effect (n=4/4). We suggest that ATP-intracellular chloride channel interactions and Mg2+ modulation of these interactions may regulate different physiological and pathological processes.
authors.affiliation: Institute of Molecular Physiology and Genetics, Centre of Excellence for Cardiovascular Research, Slovak Academy of Sciences, 83334 Bratislava, Slovakia.
authors.forename: Viera
authors.initials: V
authors.lastname: Kominkova
authors.forename: Lubica
authors.initials: L
authors.lastname: Malekova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Tomaskova
authors.forename: Peter
authors.initials: P
authors.lastname: Slezak
authors.forename: Adam
authors.initials: A
authors.lastname: Szewczyk
authors.forename: Karol
authors.initials: K
authors.lastname: Ondrias
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D008051:Lipid Bilayers; D000266:Adenylyl Imidodiphosphate; D000255:Adenosine Triphosphate; D008274:Magnesium