Calabresi P, Marfia G A, Centonze D, Pisani A, Bernardi G
Clinical Neurologica, Dip. Neuroscienze, Università di Roma Tor Vergata, Rome, Italy.
Stroke. 1999 Jan;30(1):171-9. doi: 10.1161/01.str.30.1.171.
Striatal spiny neurons are selectively vulnerable to ischemia, but the ionic mechanisms underlying this selective vulnerability are unclear. Although a possible involvement of sodium and calcium ions has been postulated in the ischemia-induced damage of rat striatal neurons, the ischemia-induced ionic changes have never been analyzed in this neuronal subtype.
We studied the effects of in vitro ischemia (oxygen and glucose deprivation) at the cellular level using intracellular recordings and microfluorometric measurements in a slice preparation. We also used various channel blockers and pharmacological compounds to characterize the ischemia-induced ionic conductances.
Spiny neurons responded to ischemia with a membrane depolarization/inward current that reversed at approximately -40 mV. This event was coupled with an increased membrane conductance. The simultaneous analysis of membrane potential changes and of variations in [Na+]i and [Ca2+]i levels showed that the ischemia-induced membrane depolarization was associated with an increase of [Na+]i and [Ca2+]i. The ischemia-induced membrane depolarization was not affected by tetrodotoxin or by glutamate receptor antagonists. Neither intracellular BAPTA, a Ca2+ chelator, nor incubation of the slices in low-Ca2+-containing solutions affected the ischemia-induced depolarization, whereas it was reduced by lowering the external Na+ concentration. High doses of blockers of ATP-dependent K+ channels increased the membrane depolarization observed in spiny neurons during ischemia.
Our findings show that, although the ischemia-induced membrane depolarization is coupled with a rise of [Na+]i and [Ca2+]i, only the Na+ influx plays a prominent role in this early electrophysiological event, whereas the increase of [Ca2+]i might be relevant for the delayed neuronal death. We also suggest that the activation of ATP-dependent K+ channels might counteract the ischemia-induced membrane depolarization.
纹状体棘状神经元对缺血具有选择性易损性，但其选择性易损性背后的离子机制尚不清楚。尽管有人推测钠和钙离子可能参与大鼠纹状体神经元的缺血性损伤，但从未对该神经元亚型缺血诱导的离子变化进行过分析。
我们在脑片标本中使用细胞内记录和显微荧光测量技术，在细胞水平研究了体外缺血（缺氧和无糖）的影响。我们还使用了各种通道阻滞剂和药理化合物来表征缺血诱导的离子电导。
棘状神经元对缺血的反应是膜去极化/内向电流，在约 -40 mV 处反转。此事件与膜电导增加相关。对膜电位变化以及 [Na⁺]i 和 [Ca²⁺]i 水平变化的同时分析表明，缺血诱导的膜去极化与 [Na⁺]i 和 [Ca²⁺]i 的增加有关。缺血诱导的膜去极化不受河豚毒素或谷氨酸受体拮抗剂的影响。细胞内 Ca²⁺ 螯合剂 BAPTA 或在低钙溶液中孵育脑片均不影响缺血诱导的去极化，而降低细胞外 Na⁺ 浓度可使其降低。高剂量的 ATP 依赖性钾通道阻滞剂增加了缺血期间棘状神经元中观察到的膜去极化。
我们的研究结果表明，尽管缺血诱导的膜去极化与 [Na⁺]i 和 [Ca²⁺]i 的升高相关，但只有 Na⁺ 内流在这一早期电生理事件中起主要作用，而 [Ca²⁺]i 的增加可能与延迟性神经元死亡有关。我们还认为，ATP 依赖性钾通道的激活可能抵消缺血诱导的膜去极化。
