Retinal voltage-dependent anion channel: Characterization and cellular localization

被引:0
作者
Gincel, D
Vardi, N
Shoshan-Barmatz, V [1 ]
机构
[1] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel
[2] Ben Gurion Univ Negev, Zlotowski Ctr Neurosci, IL-84105 Beer Sheva, Israel
[3] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA
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中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. To characterize and localize retinal voltage-dependent anion channel (VDAC) and to understand its possible contribution to mitochondrial function and dysfunction. METHODS. VDAC was characterized by a method involving purification from isolated mitochondria and reconstitution into a planar lipid bilayer (PLB). The permeability transition pore (PTP) was monitored by Ca2+ accumulation in isolated mitochondria and swelling of mitochondria. Localization was studied by immunocytochemistry and in situ hybridization. RESULTS. Retinal VDACs exhibited the electrophysiological fingerprint of the VDAC superfamily. It had a maximal chord conductance of 3.7 +/- 0.1 nanosiemens (nS) in 1 M NaCl, and a voltage-dependent conductance that was highest at transmembrane potential close to zero. It was modulated by glutamate, which decreased the channel's open probability, and by La3+ and ruthenium amine binuclear complex (Ru360), which closed the channel. Energized and freshly prepared retinal mitochondria accumulated Ca2+ that is inhibited by La3+ ruthenium, red and Ru360. Subsequent to Ca2+ accumulation, mitochondria released the accumulated Ca2+, probably through activation of the PTP. Ru360 inhibited Ca2+ release and mitochondrial swelling. VDAC was present in mitochondria of all retinal cell types: photoreceptor, bipolar, horizontal, amacrine, and ganglion cells. Most cells primarily expressed VDAC-1, but they also expressed VDAC-2 and -3. CONCLUSIONS. These results suggest that VDAC is involved in PTP activity and/or regulation and thus is an important player in retinal degeneration associated with PTP-mediated mitochondrial dysfunction.
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页码:2097 / 2104
页数:8
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