Role of sodium in mitochondrial membrane depolarization induced by P2X7 receptor activation in submandibular glands |
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| Authors: | Garcia-Marcos M Fontanils U Aguirre A Pochet S Dehaye J P Marino A |
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| Affiliation: | Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad del País Vasco, Barrio Sarriena S/N Leioa, Spain. |
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| Abstract: | The effect of ATP on mitochondrial membrane depolarization in rat submandibular glands was investigated. Exposure of the cell suspension to high concentrations of ATP induced a sustained depolarization of mitochondrial membrane. This effect was blocked in the presence of magnesium and reproduced by low concentrations of 2',3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP), suggesting the implication of the P2X(7) purinergic receptor. This point was confirmed by comparison of the response to ATP by wild-type and P2X(7) knock-out (P2X(7)R(-/-)) mice. Mitochondria took up calcium after ATP stimulation but the depolarization of the mitochondrial membrane by ATP was not affected by the removal of calcium from the extracellular medium. It was nearly fully suppressed in the absence of sodium and partially blocked by the mitochondrial Na/Ca exchanger inhibitor 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP-37157). Both ATP and monensin increased the uptake of extracellular sodium (as shown by the depolarization of the plasma membrane) but the sodium ionophore did not affect the mitochondrial membrane potential. It is concluded that the activation of P2X(7) receptors depolarizes the mitochondrial membrane. The uptake of extracellular sodium is necessary but not sufficient to induce this response. |
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| Keywords: | BzATP, 2′,3′-O-(4-benzoylbenzoyl)adenosine 5′-triphosphate BSA, bovine serum albumin TMRE, tetramethylrhodamine ethyl ester ΔΨmt, mitochondrial inner membrane potential HEPES, N-[2-hydroxyethyl] piperazine-N′-[2-ethanesulfonic acid] [Ca2+]i, intracellular concentration of calcium EGTA, ethylene glycol-bis-(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid HBS, HEPES-buffered saline FCCP, carbonyl cyanide p-(trifluoromethoxy)phenyl hydrazone NMDG, N-methyl- smallcaps" >d-glucamine PS, phosphatidylserine PTP, permeability transition pore NTP, nucleotide triphosphate Tg, thapsigargin CsA, cyclosporin A RU360, ruthenium 360 CGP-37157, 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one AIF, apoptosis inducing factor Smac/DIABLO, second mitochondrial activator of caspases/direct inhibitor of apoptosis proteins binding protein with low pI |
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