Ca(2+)-dependent non-NMDA receptor-mediated synaptic currents in ischemic CA1 hippocampal neurons.
1. The changes in excitatory postsynaptic currents (EPSCs) after transient cerebral ischemia were studied using whole-cell recording from CA1 pyramidal neurons in gerbils. In 64% (18 of 28) neurons recorded 1.5-3 days after ischemia, EPSCs showed a markedly slowed time course that was never seen in normal control neurons. 2. The slow EPSCs were not affected by an N-methyl-D-aspartate (NMDA) receptor antagonist [DL-2-aminophosphonovalerate (APV); 100 microM] but were abolished by a non-NMDA receptor antagonist [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); 10 microM], indicating that the slow EPSCs were mostly composed of non-NMDA current. 3. The slow non-NMDA EPSCs had rise times ranging from 1.2 to 7.3 ms and decay time constants between 11.5 and 56.3 ms. In normal neurons the rise time of the non-NMDA component of EPSCs ranged from 1.6 to 7.5 ms and the decay time constants ranged from 4.9 to 27.3 ms. 4. The reversal potential of the slow EPSCs in ischemic neurons was not changed by replacing 50% of the NaCl in the external solution with sodium isethionate. Bath application of 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS; 100 microM) had no effect on the slow EPSCs. Therefore Cl- current is not responsible for the slow EPSCs. 5. When external Ca2+ concentration was reduced to half of control, the decay time constant of the slow EPSCs decreased to 50 +/- 25%, mean +/- SD. In addition, bath application of a cell-permeable Ca2+ chelator, 1,2-bis(o-aminophenoxy)ethane-N,N,-N',N'-tetraacetyl,tetr aacetoxymethyl ester(BAPTA-AM), reduced the decay time constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Tsubokawa
H
H
Department of Physiology, Jichi Medical School, Tochigi-ken, Japan.
Oguro
K
K
Masuzawa
T
T
Kawai
N
N
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology; D005071:Evoked Potentials / Q000502:physiology; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply* / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000502:physiology; D009474:Neurons / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D015220:Calcium Channels; D018118:Chloride Channels; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate