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This Article Full Text Full Text (PDF) All Versions of this Article: 285/1/C119    most recent 00296.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science 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 Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Bull, R. Articles by Alvarez, O. Search for Related Content PubMed PubMed Citation Articles by Bull, R. Articles by Alvarez, O.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

SH oxidation coordinates subunits of rat brain ryanodine receptor channels activated by calcium and ATP

¹Programa de Fisiología y Biofísica and ²Programa de Patología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 838-0453; ³Servicio de Neurología, Hospital Sótero del Río, Santiago 820-7257; and ⁴Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile 780-0024

Submitted 25 June 2002 ; accepted in final form 4 March 2003

We have reported that ryanodine receptor (RyR) channels display three different responses to cytoplasmic free Ca²⁺ concentration ([Ca²⁺]) depending on their redox state (Marengo JJ, Hidalgo C, and Bull R. Biophys J 74: 1263–1277, 1998), with low, moderate, and high maximal fractional open times (P_o). Activation by ATP of single RyR channels from rat brain cortex was tested in planar lipid bilayers with 10 or 0.1 µM cytoplasmic [Ca²⁺]. At 10 µM [Ca²⁺], low-P_o channels presented lower apparent affinity to activation by ATP [[ATP] for half-maximal activation (K_aATP) = 422 µM] than moderate-P_o channels (K_aATP = 82 µM). Oxidation of low-P_o channels with thimerosal or 2,2'-dithiodipyridine (DTDP) gave rise to moderate-P_o channels and decreased K_aATP from 422 to 82 µM. At 0.1 µM cytoplasmic [Ca²⁺], ATP induced an almost negligible activation of low-P_o channels. After oxidation to high-P_o behavior, activation by ATP was markedly increased. Noise analysis of single-channel fluctuations of low-P_o channels at 10 µM [Ca²⁺] plus ATP revealed the presence of subconductance states, suggesting a conduction mechanism that involves four independent subchannels. On oxidation the subchannels opened and closed in a concerted mode.

subconductance states; calcium ion release channels; calcium ion regulation; thimerosal; 2,2'-dithiodipyridine

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