Effects of mitochondrial uncouplers on intracellular calcium, pH and membrane potential in rat carotid body type I cells
Effects of mitochondrial uncouplers on intracellular calcium, pH and membrane potential in rat carotid body type I cells
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DOI：
10.1111/j.1469-7793.1998.819ba.x
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发表时间：
1998-12-15
影响因子：
5.5
通讯作者：
Vaughan-Jones, RD
中科院分区：
文献类型：
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作者：
Buckler, KJ;Vaughan-Jones, RD
1.线粒体解偶联剂是颈动脉体的有效兴奋剂。因此，我们研究了它们对分离的I型细胞的影响。2，4-二硝基苯酚（DNP）和羰基氰对三氟甲氧基苯腙（FCCP）均引起[Ca ~（2+）]（i）的增加，而去除细胞外Ca ~（2+）或Na ~+或加入2 mM Ni ~（2+）可大大抑制[Ca ~（2+）]（i）的增加。甲氧维拉帕米（D 600）也部分抑制[Ca 2 +]（i）反应.在穿孔膜片记录中，[Ca 2 +]（i）的升高与膜去极化一致，并通过将细胞电压钳位至-70 mV而大大降低。解偶联剂也抑制了背景K+电流，并诱导了一个小的内向电流.解偶联剂使pH（i）降低0.1单位。碱性介质减弱了这种酸化作用，但对[Ca 2 +]（1）响应没有影响. FCCP和DNP也使I型细胞线粒体去极化。线粒体去极化的发生先于细胞膜电导的变化3-4秒。5.我们的结论是，解偶联剂通过抑制背景K+电导和诱导小的内向电流，这两个导致膜去极化和电压门控Ca 2+进入，兴奋颈动脉体。这些影响不太可能是由细胞酸化引起的。背景K+电流的抑制可能与氧化磷酸化解偶联有关。
1. Mitochondrial uncouplers are potent stimulants of the carotid body. We have therefore investigated their effects upon isolated type I cells. Both 2,4-dinitrophenol (DNP) and carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP) caused an increase in [Ca2+](i) which was largely inhibited by removal of extracellular Ca2+ or Na+, or by the addition of 2 mM Ni2+. Methoxyverapamil (D600) also partially inhibited the [Ca2+](i) response.2. In perforated-patch recordings, the rise in [Ca2+](i) coincided with membrane depolarization and was greatly reduced by voltage clamping the cell to -70 mV. Uncouplers also inhibited a background K+ current and induced a small inward current.3. Uncouplers reduced pH(i) by 0.1 unit. Alkaline media diminished this acidification but had no effect on the [Ca2+](1) response.4. FCCP and DNP also depolarized type I cell mitochondria. The onset of mitochondrial depolarization preceded changes in cell membrane conductance by 3-4 s.5. We conclude that uncouplers excite the carotid body by inhibiting a background K+ conductance and inducing a small inward current, both of which lead to membrane depolarization and voltage-gated Ca2+ entry. These effects are unlikely to be caused by cell acidification. The inhibition of background K+ current may be related to the uncoupling of oxidative phosphorylation.