Differential effects of Na-K-ATPase pump inhibition, chemical anoxia, and glycolytic blockade on membrane potential of rat optic nerve.
Differential effects of Na-K-ATPase pump inhibition, chemical anoxia, and glycolytic blockade on membrane potential of rat optic nerve.
复制标题
Na-K-ATP酶泵抑制、化学缺氧和糖酵解阻断对大鼠视神经膜电位的不同影响。
DOI：
10.1016/j.brainres.2005.01.003
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发表时间：
2005
期刊：
影响因子：
2.9
通讯作者：
Stys,PK
中科院分区：
文献类型：
--
作者：
Malek,SA;Adorante,JS;Stys,PK
在缺氧或哇巴因灌流过程中，Na+-K+-ATPase泵衰竭可通过消散离子梯度而导致轴突快速去极化。在本研究中，我们研究了在缺氧或选择性抑制Na+-K+-ATPase的过程中，阳离子和阴离子转运通路之间的相互作用。大鼠视神经复合静息膜(Vm)电位在37°C的油脂缝隙中测定。化学缺氧(2 mM NaCN或NaN3)或哇巴因(1 MM)使视神经静息电位在30min后分别下降至对照组的42±11%和47±2%。电压门控性钠通道阻断可部分消除这种去极化作用。河豚毒素(1μM)使去极化程度降低至对照组的73±10%和68±4%。季胺钠通道阻滞剂QX-314(1 MM)或普吉马林(100μM)也有类似的结果。一种广谱阴离子转运阻滞剂DIDS(500μM)进一步避免了化学缺氧时K+和Cl-Tx的共同外流的残余离子流失(缺氧+河豚毒素30min后为对照的95±8%，而单独河豚毒素为73±10%)。在哇巴因中，加入DIDS的疗效略高于TTX(74±5%DIDS+TTX对68±4%的TTX，P<；0.05)。在哇巴因诱导的去极化过程中，使用布美他尼研究了其他Na+进入途径，如Na-K-Cl共转运体，它产生了少量的Vm，尽管有显著的减少。虽然阳离子转运途径在中枢轴突病理性去极化中发挥了更重要的作用，但阴离子偶联转运体也在很大程度上起到了作用，尽管程度较小。
Na+-K+-ATPase pump failure during either anoxia or ouabain perfusion induces rapid axonal depolarization by dissipating ionic gradients. In this study, we examined the interplay between cation and anion transporting pathways mediating axonal depolarization during anoxia or selective Na+-K+-ATPase inhibition. Compound resting membrane (Vm) potential of rat optic nerve was measured in a grease gap at 37 °C. Chemical anoxia (2 mM NaCN or NaN3) or ouabain (1 mM) caused a loss of resting potential to 42 ± 11% and 47 ± 2% of control after 30 min, respectively. Voltage-gated Na+-channel blockade was partially effective in abolishing this depolarization. TTX (1 μM) reduced depolarization to 73 ± 10% (chemical anoxia) and 68 ± 4% (ouabain) of control. Quaternary amine Na+channel blockers QX-314 (1 mM) or prajmaline (100 μM) produced similar results. Residual ionic rundown largely representing co-efflux of K+and Cl−during chemical anoxia in the presence of Na+-channel blockade was further spared with DIDS (500 μM), a broad-spectrum anion transport inhibitor (95 ± 8% of control after 30 min in anoxia + TTX vs. 73 ± 10% in TTX alone). Addition of DIDS was slightly more effective than TTX alone in ouabain (74 ± 5% DIDS + TTX vs. 68 ± 4% in TTX alone, P < 0.05). Additional Na+-entry pathways such as the Na-K-Cl cotransporter were examined using bumetanide, which produced a modest albeit significant sparing of Vmduring ouabain-induced depolarization. Although cation-transporting pathways play the more important role in mediating pathological depolarization of central axons, anion-coupled transporters also contribute to a significant, albeit more minor, degree.