TWO FORMS OF LONG-TERM POTENTIATION IN AREA CA1 ACTIVATE DIFFERENT SIGNAL TRANSDUCTION CASCADES. Cavu, Idil & Tim Teyler. Neurobiology Department, Northeastern Ohio Universities College of Medicine, 4209 State Rt. 44, P.O. Box 95, Rootstown, OH 44274-0095, U.S.A.
APStracts 3:0146N, 1996.
1. The effects of protein kinase inhibitors on N-methyl- D -aspartate (NMDA) receptor-mediated, voltage-dependent calcium channel (VDCC)-mediated and 100 Hz long-term potentiation (LTP) were studied in area CA1 of rat hippocampal slices. 2. Twenty five Hz tetanus induced a quickly developing potentiation that was blocked by the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (APV) and was not affected by the L-type VDCC inhibitor nifedipine, suggesting that it was mediated by NMDA receptors (NMDA-LTP). 3. Application of 200 Hz tetanus in APV induced a slowly developing NMDA receptor-independent potentiation which was blocked by nifedipine, and hence named VDCC-LTP. NMDA- and VDCC-LTP reached comparable magnitudes despite their different induction parameters and developmental kinetics. 4. Bath perfusion of broad spectrum serine/threonine kinase inhibitor H-7 blocked NMDA-LTP but not VDCC-LTP, whereas the tyrosine kinase inhibitors genistein and lavendustin A blocked VDCC-LTP, but not NMDA-LTP. These results suggest a differential involvement of H-7-sensitive serine/threonine kinases and tyrosine kinases in the two forms of LTP. 5. Tetanization with 200 Hz in control media resulted in a compound potentiation twice as large as NMDA- or VDCC-LTP, implying that the two forms of LTP did not facilitate or reduce each other's expression. The often used 100 Hz tetanus (1 sec twice) induced a potentiation which was comparable in size to the 200 Hz compound LTP. Nifedipine, genistein and lavendustin A reduced the 100 Hz LTP by approximately 50 %, suggesting that this LTP is also a compound potentiation consisting of NMDA- and VDCC-mediated components and their corresponding signal transduction pathways.

Received 9 May 1996; accepted in final form 27 June 1996.
APS Manuscript Number J382-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996