Examination of TEA-induced synaptic enhancement in area CA1 of the hippocampus: the role of voltage-dependent Ca2+ channels in the induction of LTP.
The role of voltage-dependent Ca2+ channels (VDCCs) in the induction of long-term potentiation (LTP) in the CA1 region of rat hippocampus was determined by examining the relationship between LTP and the long-lasting synaptic enhancement induced by extracellular application of tetraethylammonium (TEA). Consistent with previous findings (Aniksztejn and Ben-Ari, 1991), the TEA-induced synaptic enhancement did not require NMDA receptor activation. It was blocked by the L-type VDCC antagonist nifedipine or by intracellular injection of the Ca2+ chelator 1,2-bis(2-amino-phenoxy)ethane N,N,N',N'-tetra-acetic acid (BAPTA) and could be mimicked by direct activation of VDCCs with repetitive depolarizing current pulses. In contrast to its effect on TEA-induced synaptic enhancement, nifedipine had no effect on the magnitude or duration of NMDA receptor-dependent LTP. Saturation of NMDA receptor-dependent LTP reduced the magnitude of the TEA-induced synaptic enhancement. Similarly, increasing synaptic strength by initial application of TEA reduced the magnitude of the subsequent tetanus-induced LTP. Like LTP, the TEA-induced synaptic enhancement did not significantly affect paired-pulse facilitation. These results suggest that dihydropyridine-sensitive VDCCs do not normally contribute to the induction of NMDA receptor-dependent LTP even though their repetitive activation can generate an increase in synaptic strength. The mutual occlusion of LTP and TEA-induced synaptic enhancement suggests that they share a common expression mechanism and perhaps are generated by activation of common Ca(2+)-dependent intracellular processes.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Psychiatry, University of California, San Francisco 94143.
Y Y
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Huang
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Malenka
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D013757:Tetraethylammonium Compounds; D004533:Egtazic Acid; D019789:Tetraethylammonium; D009543:Nifedipine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid