Wang Y, Rowan M J, Anwyl R
Department of Physiology, Trinity College, Dublin 2, Ireland.
J Neurophysiol. 1997 Nov;78(5):2574-81. doi: 10.1152/jn.1997.78.5.2574.
LTP induction dependent on activation of Ni2+-sensitive voltage-gated calcium channels, but not NMDA receptors, in the rat dentate gyrus in vitro. J. Neurophysiol. 78: 2574-2581, 1997. A N-methyl--aspartate receptor (NMDAR)-independent long-term potentiation (LTP) has been investigated in the dentate gyrus of the hippocampus in vitro in the presence of the NMDAR antagonist, -2-amino-phosphonopentanoate (50-100 mu M), at a concentration that completely blocked NMDAR-mediated excitatory postsynaptic currents (EPSCs). LTP of patch-clamped EPSCs was induced by pairing low-frequency evoked EPSCs (1 Hz) with depolarizing voltage pulses designed to predominately open low-voltage-activated (LVA) Ca2+ channels. Voltage pulses alone induced only a short-term potentiation. The LTP was blocked by intracellular application of the rapid Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid, demonstrating that a rise in intracellular Ca2+ is required for the NMDAR-independent LTP induction. The NMDAR-independent LTP induction also was blocked by Ni2+ at a low extracellular concentration (50 mu M), which is known to strongly block LVA Ca2+ channels. However, Ni2+ did not inhibit the NMDAR-dependent LTP induced by high-frequency stimulation (HFS). The NMDAR-independent LTP induction was not blocked by high concentrations of the L-type Ca2+ channel blocker nifedipine (10 mu M). The NMDAR-independent LTP was inhibited by the metabotropic glutamate receptor ligand (+)-alpha-methyl-4-carboxyphenylglycine. These experiments demonstrate the presence of a NMDAR-independent LTP induced by Ca2+ influx via Ni2+-sensitive, nifedipine-insensitive voltage-gated Ca2+ channels, probably LVA Ca2+ channels. Induction of the NMDAR-independent LTP was inhibited by prior induction of HFS-induced NMDAR-dependent LTP, demonstrating that although the NMDAR-dependent and NMDAR-independent LTP use a different Ca2+ channel for Ca2+ influx, they share a common intracellular pathway.
体外培养的大鼠齿状回中，长时程增强（LTP）的诱导依赖于镍离子敏感的电压门控钙通道的激活，而非N-甲基-D-天冬氨酸受体（NMDA受体）。《神经生理学杂志》78: 2574 - 2581, 1997年。在存在NMDA受体拮抗剂-2-氨基-5-膦酰基戊酸（50 - 100 μM）的情况下，已对体外培养的海马齿状回中不依赖NMDA受体的长时程增强（LTP）进行了研究，该浓度可完全阻断NMDA受体介导的兴奋性突触后电流（EPSCs）。通过将低频诱发的EPSCs（1 Hz）与旨在主要打开低电压激活（LVA）Ca2+通道的去极化电压脉冲配对，诱导膜片钳记录的EPSCs的LTP。单独的电压脉冲仅诱导短期增强。细胞内应用快速Ca2+螯合剂双（邻氨基苯氧基）-N,N,N',N'-四乙酸可阻断LTP，表明细胞内Ca2+升高是不依赖NMDA受体的LTP诱导所必需的。低细胞外浓度（50 μM）的镍离子也可阻断不依赖NMDA受体的LTP诱导，已知镍离子可强烈阻断LVA Ca2+通道。然而，镍离子并不抑制高频刺激（HFS）诱导的依赖NMDA受体的LTP。高浓度的L型钙通道阻滞剂硝苯地平（10 μM）不能阻断不依赖NMDA受体的LTP诱导。代谢型谷氨酸受体配体（+）-α-甲基-4-羧基苯甘氨酸可抑制不依赖NMDA受体的LTP。这些实验证明存在一种不依赖NMDA受体的LTP，其通过镍离子敏感、硝苯地平不敏感的电压门控钙通道（可能是LVA Ca2+通道）内流Ca2+诱导产生。预先诱导HFS诱导的依赖NMDA受体的LTP可抑制不依赖NMDA受体的LTP的诱导，表明尽管依赖NMDA受体和不依赖NMDA受体的LTP使用不同的Ca2+通道进行Ca2+内流，但它们共享一条共同的细胞内途径。
