Energetic performance is improved by specific activation of K+ fluxes through K(Ca) channels in heart mitochondria.
Energetic performance is improved by specific activation of K+ fluxes through K(Ca) channels in heart mitochondria.
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DOI：
10.1016/j.bbabio.2009.08.002
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发表时间：
2010-01
影响因子：
4.3
通讯作者：
O'Rourke, Brian
中科院分区：
文献类型：
--
作者：
Aon, Miguel A.;Cortassa, Sonia;Wei, An-Chi;Grunnet, Morten;O'Rourke, Brian
关键词：
线粒体容积调节依赖于K+穿过内膜的运动，据报道线粒体Ca 2+依赖性K+通道（mitoKCa）有助于线粒体K+单向转运体活性。在这里，我们利用一种新的KCa通道激活剂，NS 11021，通过测量豚鼠心脏线粒体的K+通量，膜电位（Δ Km），光散射和呼吸来研究mitoKCa在调节线粒体功能中的作用。通过在蔗糖基培养基中向供能的线粒体中加入K+的氯化物（KCl）、乙酸盐（KAc）或磷酸盐（KH 2 PO 4）来评估负载有K+传感器PBFI的线粒体中的K+摄取和阴离子的影响。每种盐的K+通量在~ 10 mM时达到饱和，在KCl、KAc或KH 2 PO 4中分别达到172±17、54±2.4和33±3.8 nmol K+/min/mg的最大速率。NS 11021（50 nM）在KH 2 PO 4或KAc存在下使最大K+摄取速率增加2.5倍，并增加线粒体体积，对Δ Δ Km几乎没有影响。在KCl中，NS 11021仅增加了30%的K+吸收，并且没有增加体积。NS 11021对K+吸收的影响被KCa毒素Charybdotoxin（200 nM）或paxilline（1μM）抑制。50 nM NS 11021增加了KH 2 PO 4中的线粒体呼吸控制率（RCR），但在KCl中不增加;然而，高于1μM时，NS 11021降低了RCR和去极化Δ λ m。缺乏KCa激活剂特性的对照化合物不增加K+摄取或体积，但在高浓度下具有类似的非特异性（毒素不敏感）作用。结果表明，通过mitoKCa激活K+通量介导了对能量学的有益影响，该能量学依赖于线粒体肿胀并维持Δ m。
Mitochondrial volume regulation depends on K+ movement across the inner membrane and a mitochondrial Ca2+-dependent K+ channel (mitoKCa) reportedly contributes to mitochondrial K+ uniporter activity. Here we utilize a novel KCa channel activator, NS11021, to examine the role of mitoKCa in regulating mitochondrial function by measuring K+ flux, membrane potential (ΔΨm), light scattering, and respiration in guinea-pig heart mitochondria. K+ uptake and the influence of anions were assessed in mitochondria loaded with the K+ sensor PBFI by adding either the chloride (KCl), acetate (KAc) or phosphate (KH2PO4) salts of K+ to energized mitochondria in a sucrose-based medium. K+ fluxes saturated at ~10mM for each salt, attaining maximal rates of 172±17, 54±2.4 and 33±3.8 nmol K+/min/mg in KCl, KAc or KH2PO4, respectively. NS11021 (50nM) increased the maximal K+ uptake rate by 2.5- fold in the presence of KH2PO4 or KAc, and increased mitochondrial volume, with little effect on ΔΨm. In KCl, NS11021 increased K+ uptake by only 30% and did not increase volume. The effects of NS11021 on K+ uptake were inhibited by the KCa toxins charybdotoxin (200nM) or paxilline (1μM). 50nM NS11021 increased the mitochondrial respiratory control ratio (RCR) in KH2PO4, but not in KCl; however, above 1μM, NS11021 decreased RCR and depolarized ΔΨm. A control compound lacking KCa activator properties did not increase K+ uptake or volume, but had similar nonspecific (toxin insensitive) effects at high concentrations. The results indicate that activating K+ flux through mitoKCa mediates a beneficial effect on energetics that depends on mitochondrial swelling with maintained ΔΨm.
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影响因子：
4.3
作者：
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通讯作者：
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影响因子：
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