Skov Jane, Nedergaard Steen, Andreasen Mogens
Institute of Physiology and Biophysics, Deptartment of Physiology, University of Aarhus, DK-8000 Aarhus C, Denmark.
J Neurophysiol. 2005 Apr;93(4):1845-56. doi: 10.1152/jn.00656.2004. Epub 2004 Nov 10.
It is well known that excitatory synaptic transmission at the hippocampal CA3-CA1 synapse depends on the binding of released glutamate to ionotropic receptors. Here we report that during long-term application of Cs+ (5 mM), stimulation of the Schaffer collateral-commisural pathway evokes an epileptic field potential (Cs-FP) in area CA1 of the rat hippocampal slice, which is resistant to antagonists of ionotropic glutamate and GABA(A) receptors. The Cs-FP was blocked by N-type but not L-type Ca2+ channel antagonists and was attenuated by adenosine (0.5 mM), as expected for a synaptically mediated response. These properties make the Cs-FP fundamentally different from other types of Cs(+)-induced epileptiform activity. Replacement of Cs+ with antagonists of the hyperpolarization-activated nonselective cation current I(h) and inwardly rectifying potassium channels (K(IR)) or partial inhibition of the Na(+)/K+ pump did not cause Cs-FP-like potentials, which indicates that such actions of Cs+ were not responsible for the Cs-FP. The effect of Cs+ was partly mimicked by 4-aminopyridine (4-AP; 2 mM), suggesting that an increase in transmitter release is involved. The group I metabotropic glutamate receptor (mGluR) agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) attenuated the Cs-FP. This effect was not, however, antagonized by group I mGluR antagonists. Selective and nonselective mGluR antagonists did not attenuate the Cs-FP. We conclude that long-term exposure to Cs+ induces a state where excitatory synaptic transmission can exist between area CA3 and CA1 in the hippocampus, independent of ionotropic and metabotropic glutamate receptors and GABA(A) receptors.
众所周知，海马体CA3-CA1突触处的兴奋性突触传递依赖于释放的谷氨酸与离子型受体的结合。在此我们报告，在长期应用Cs+（5 mM）期间，刺激海马体-连合通路在大鼠海马体切片的CA1区诱发癫痫场电位（Cs-FP），该电位对离子型谷氨酸和GABAA受体拮抗剂具有抗性。Cs-FP被N型而非L型Ca2+通道拮抗剂阻断，并被腺苷（0.5 mM）减弱，这与突触介导的反应预期一致。这些特性使Cs-FP与其他类型的Cs+诱导的癫痫样活动有根本区别。用超极化激活的非选择性阳离子电流I(h)和内向整流钾通道（K(IR)）的拮抗剂替代Cs+或部分抑制Na+/K+泵不会引起类似Cs-FP的电位，这表明Cs+的此类作用与Cs-FP无关。4-氨基吡啶（4-AP；2 mM）部分模拟了Cs+的作用，表明涉及递质释放增加。I组代谢型谷氨酸受体（mGluR）激动剂（RS）-3,5-二羟基苯甘氨酸（DHPG）减弱了Cs-FP。然而，这种作用并未被I组mGluR拮抗剂拮抗。选择性和非选择性mGluR拮抗剂均未减弱Cs-FP。我们得出结论，长期暴露于Cs+会诱导一种状态，即海马体CA三区域和CA1区域之间可存在兴奋性突触传递，且不依赖于离子型和代谢型谷氨酸受体以及GABAA受体。
