Differential maturation of GABA action and anion reversal potential in spinal lamina I neurons: Impact of chloride extrusion capacity
Differential maturation of GABA action and anion reversal potential in spinal lamina I neurons: Impact of chloride extrusion capacity
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DOI：
10.1523/jneurosci.1488-05.2005
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发表时间：
2005-10-19
影响因子：
5.3
通讯作者：
De Koninck, Y
中科院分区：
文献类型：
--
作者：
Cordero-Erausquin, M;Coull, JAM;De Koninck, Y
脊髓背角抑制缺陷被认为是新生大鼠皮肤感觉反射过度的根本原因。然而，跨膜阴离子梯度的发育变化可能会影响 GABA(A) 传递的结果，该变化被证明在出生后 1 周内在脊髓中完成，这与反射超敏反应在出生后 2-3 周持续存在的观察结果明显不一致。为了进一步研究这个问题，我们使用了几种方法来评估 GABA 在脊髓板 I (LI) 神经元整个发育过程中的作用。从出生后第 0 天 (P0) 到 P21 大鼠，GABA 诱导 LI 神经元细胞外钙进入，其中涉及 T 型和 N 型电压门控钙通道。短杆菌肽穿孔贴片记录显示，阴离子梯度的变化是由 LI 神经元中的 P7 完成的。然而，高氯移液器记录表明这些神经元在 P10-P11 时尚未达到其成年氯排出能力。同时膜片钳记录和钙成像显示，对 GABA 的双相反应（包括初级超极化和反弹去极化）导致 [Ca2+](i) 升高。因此，即使 E-阴离子预测 GABA(A) 诱导的静息超极化，低氯排出能力也会导致去极化反弹和 [Ca2+](i) 随之增加。我们证明 LI 神经元中的 GABA 作用在出生后前 3 周内成熟，因此与撤回反射成熟的时间过程相匹配。因此，不成熟的脊髓 GABA 信号传导可能导致幼年大鼠的伤害性超敏反应。
A deficit in inhibition in the spinal dorsal horn has been proposed to be an underlying cause of the exaggerated cutaneous sensory reflexes observed in newborn rats. However, the developmental shift in transmembrane anion gradient, potentially affecting the outcome of GABA(A) transmission, was shown to be completed within 1 week after birth in the spinal cord, an apparent disparity with the observation that reflex hypersensitivity persists throughout the first 2-3 postnatal weeks.To further investigate this issue, we used several approaches to assess the action of GABA throughout development in spinal lamina I (LI) neurons. GABA induced an entry of extracellular calcium in LI neurons from postnatal day 0 (P0) to P21 rats, which involved T- and N-type voltage-gated calcium channels. Gramicidin perforated-patch recordings revealed that the shift in anion gradient was completed by P7 in LI neurons. However, high chloride pipette recordings demonstrated that these neurons had not reached their adult chloride extrusion capacity by P10-P11. Simultaneous patch-clamp recordings and calcium imaging revealed that biphasic responses to GABA, consisting of a primary hyperpolarization followed by a rebound depolarization, produced a rise in [Ca2+](i). Thus, even if E-anion predicts GABA(A)- induced hyperpolarization from rest, a low chloride extrusion capacity can cause a rebound depolarization and an ensuing rise in [Ca2+](i).We demonstrate that GABA action in LI neurons matures throughout the first 3 postnatal weeks, therefore matching the time course of maturation of withdrawal reflexes. Immature spinal GABA signaling may thus contribute to the nociceptive hypersensitivity in infant rats.