New type of synaptically mediated epileptiform activity independent of known glutamate and GABA receptors.
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.
Skov
Jane
J
Institute of Physiology and Biophysics, Deptartment of Physiology, University of Aarhus, DK-8000 Aarhus C, Denmark.
Nedergaard
Steen
S
Andreasen
Mogens
M
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004827:Epilepsy / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D018079:Receptors, GABA; D017470:Receptors, Glutamate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione