Induction of the Non-selective Mitochondrial Pore in Lymphoid Cells. 1. Permeabilized Rat Thymocytes

B. V. Chernyak

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (095) 939-3181; E-mail: chernyak@pcman.genebee.msu.su

Received December 8, 1998; Revision received March 1, 1999

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The opening of the cyclosporin-sensitive pore in the inner membrane of mitochondria in rat thymocytes was studied. In thymocytes with digitonin-permeabilized plasma membrane, the mitochondrial pore was induced by Ca²⁺ overload, by uncoupling, by oxidation or cross-linking of membrane dithiols, and by atractyloside, a specific inhibitor of the adenine nucleotide transporter. Pore opening was prevented by cyclosporin A (CsA) and by its non-immunosuppressive analog MeVal-CsA. The sensitivity of the pore to CsA was decreased by atractyloside and practically disappeared when it was added in combination with uncoupler. The main properties of the pore in mitochondria from thymocytes and from hepatocytes are the same. Release of Ca²⁺ from thymocyte mitochondria induced by uncoupling is mediated by a specific uniporter and by the pore with similar rates.

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KEY WORDS: thymocytes, mitochondria, Ca²⁺ release, cyclosporin-sensitive pore, pro-oxidants, SH-reagents, atractyloside, uncoupling

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