Modulation of spreading depression by changes in extracellular pH.
Modulation of spreading depression by changes in extracellular pH.
复制标题
通过改变细胞外 pH 值来调节抑郁的扩散。
DOI：
10.1152/jn.2000.84.5.2449
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Chesler,M
中科院分区：
文献类型：
--
作者：
Tong,CK;Chesler,M
扩散性抑郁（SD）及其相关现象与缺氧缺血性损伤有关。在这种情况下，SD会出现明显的细胞外酸中毒。SD本身也可以引起细胞外pH （pHo）的变化，包括明显的早期碱性转移。在海马切片模型中，我们研究了间质酸中毒对CA1辐射层SD产生和繁殖的影响。此外，用碳酸酐酶抑制剂（苯唑胺）减少碱性转移的缓冲，以研究其对SD的调节作用。ph值的降低是由于盐水HCO3−的减少（在5% CO2条件下从26到13到6.5 mM）或CO2含量的增加（在26 mM HCO3−条件下从5到15%）。pH微电极记录pH值分别为7.23±0.13、6.95±0.10、6.67±0.09和6.97±0.12。酸中毒的总体影响是SD诱导阈值升高，速度降低，SD持续时间缩短。这种抑制在最低pHo（6.5 mM HCO3−）时最为明显，此时SD通常被阻断。酸中毒的影响在恢复生理盐水后是可逆的。苯甲酰胺（10 μM）使早期碱性位移增加了近一倍，达到0.3-0.4 U ph的幅度。放大的碱中毒与波的持续时间和/或速度增加有关。这些效果在酸性介质（13 mM HCO3−/5% CO2）中最为明显，苯并胺使SD持续时间延长55±32%。初始速度（包括诱导时间）和传播速度（在远端电极之间测量）分别提高了35±25和26±16%。[Ca2+]的测量表明，在钙瞬态的持续时间的增加，当碱性转移被苯甲酰胺放大。在含有n -甲基-d-天冬氨酸（NMDA）受体拮抗剂- 2-氨基-5-磷酸戊酸的培养基中，苯甲酰胺引起的SD增强被阻断。这些数据表明，缺血条件下基线pH值的下降会抑制SD的诱导和繁殖，而早期的碱性转移可以通过减轻NMDA受体上的质子阻断来消除这种抑制。在缺血条件下，内禀碱中毒可能导致SD，从而导致NMDA受体介导的损伤。
Spreading depression (SD) and related phenomena have been implicated in hypoxic-ischemic injury. In such settings, SD occurs in the presence of marked extracellular acidosis. SD itself can also generate changes in extracellular pH (pHo), including a pronounced early alkaline shift. In a hippocampal slice model, we investigated the effect of interstitial acidosis on the generation and propagation of SD in the CA1 stratum radiatum. In addition, a carbonic anhydrase inhibitor (benzolamide) was used to decrease buffering of the alkaline shift to investigate its role in the modulation of SD. pHowas lowered by a decrease in saline HCO3−(from 26 to 13 to 6.5 mM at 5% CO2), or by an increase in the CO2content (from 5 to 15% in 26 mM HCO3−). Recordings with pH microelectrodes revealed respective pHo values of 7.23 ± 0.13, 6.95 ± 0.10, 6.67 ± 0.09, and 6.97 ± 0.12. The overall effect of acidosis was an increase in the threshold for SD induction, a decrease in velocity, and a shortened SD duration. This inhibition was most pronounced at the lowest pHo(in 6.5 mM HCO3−) where SD was often blocked. The effects of acidosis were reversible on return to control saline. Benzolamide (10 μM) caused an approximate doubling of the early alkaline shift to an amplitude of 0.3–0.4 U pH. The amplified alkalosis was associated with an increased duration and/or increased velocity of the wave. These effects were most pronounced in acidic media (13 mM HCO3−/5% CO2) where benzolamide increased the SD duration by 55 ± 32%. The initial velocity (including time for induction) and propagation velocity (measured between distal electrodes) were enhanced by 35 ± 25 and 26 ± 16%, respectively. Measurements of [Ca2+]odemonstrated an increase in duration of the Ca2+transient when the alkaline shift was amplified by benzolamide. The augmentation of SD caused by benzolamide was blocked in media containing theN-methyl-d-aspartate (NMDA) receptor antagonistdl−2-amino-5-phosphonovaleric acid. These data indicate that the induction and propagation of SD is inhibited by a fall in baseline pH characteristic of ischemic conditions and that the early alkaline shift can remove this inhibition by relieving the proton block on NMDA receptors. Under ischemic conditions, the intrinsic alkalosis may therefore enable SD and thereby contribute to NMDA receptor-mediated injury.