Danober L, Pape H C
Institut für Physiologie, Medizinische Fakultät, Otto-von-Guericke-Universität, Magdeburg, Germany.
Eur J Neurosci. 1998 Mar;10(3):853-67. doi: 10.1046/j.1460-9568.1998.00092.x.
A slow inhibitory potential (sIP) elicited upon synaptic activation in spiny, pyramidal-like cells with properties indicative of projection neurons was investigated in slices of the rat and guinea-pig lateral amygdala in vitro. The sIP succeeded the triphasic sequence of excitatory and fast/slow inhibitory postsynaptic potentials mediated via glutamate and GABA(A/B) receptors, respectively, was readily evoked upon repetitive stimulation of the external capsule and appeared to terminate epileptiform burst discharges during pharmacologically reduced GABAergic influence. The sIP reversed close to the Cl- equilibrium potential, but was not affected by altered transmembrane Cl- gradients and not abolished by antagonists to ligand-gated Cl- channels. Intracellular injection of QX 314 and resulting blockade of sodium spikes had no effect, whereas the Ca2+ chelator BAPTA blocked the sIP concomitantly with slow hyperpolarizing afterpotentials following intrinsically generated spike firing, thereby indicating the contribution of Ca2+-dependent mechanisms secondary to synaptic activation. During action of BAPTA and QX 314, an N-methyl-D-aspartate (NMDA) receptor-mediated potential was unmasked, which contributed to the sIP. The Ca2+-dependent mechanisms of the sIP involved a membrane K+ conductance, as was indicated by the dependence on the K+ gradient and the shift of the reversal potential towards the K+ equilibrium potential during blocked NMDA receptors. During the presence of GABA receptor antagonists, reduction of the Ca2+-activated K+ conductance through injection of BAPTA or application of dopamine induced a gradual shift of interictal-like single bursts of spikes towards the generation of re-occurring ictal-like activity. It is concluded that pyramidal-like projection cells in the AL can generate a sIP upon synaptic activation, which reflects the combined activation of an NMDA receptor-mediated cation current and a K+ current that is secondary to the rise in intracellular Ca2+ concentration resulting from the preceding depolarizing response. The sIP may play an important role in controlling excitatory activity in the amygdala, particularly in preventing the transformation of interictal-like activity towards recurrent epileptic discharges during periods of decreased GABAergic influence.
在体外培养的大鼠和豚鼠外侧杏仁核切片中，研究了在具有投射神经元特征的棘状、锥体形细胞突触激活时引发的慢抑制电位（sIP）。sIP在分别由谷氨酸和GABA（A/B）受体介导的兴奋性和快/慢抑制性突触后电位的三相序列之后出现，在重复刺激外囊时很容易诱发，并且在药理学上降低GABA能影响期间似乎终止癫痫样爆发放电。sIP在接近Cl-平衡电位时反转，但不受跨膜Cl-梯度改变的影响，也不被配体门控Cl-通道拮抗剂所消除。细胞内注射QX 314并由此阻断钠峰电位没有影响，而Ca2+螯合剂BAPTA在内在产生的峰电位发放后的慢超极化后电位同时阻断了sIP，从而表明突触激活后Ca2+依赖性机制的作用。在BAPTA和QX 314作用期间，一种N-甲基-D-天冬氨酸（NMDA）受体介导的电位被揭示出来，它对sIP有贡献。sIP的Ca2+依赖性机制涉及膜K+电导，这由对K+梯度的依赖性以及在阻断NMDA受体期间反转电位向K+平衡电位的偏移所表明。在存在GABA受体拮抗剂的情况下，通过注射BAPTA或应用多巴胺降低Ca2+激活的K+电导会导致间歇性样单个峰电位爆发逐渐向复发性癫痫样活动的产生转变。结论是，杏仁核中的锥体形投射细胞在突触激活时可产生sIP，这反映了NMDA受体介导的阳离子电流和由于先前去极化反应导致细胞内Ca2+浓度升高继发的K+电流的联合激活。sIP可能在控制杏仁核中的兴奋性活动中起重要作用，特别是在GABA能影响降低期间防止间歇性样活动向复发性癫痫放电的转变。
