MECHANISMS OF POTENTIATION BY CALCIUM-CALMODULIN KINASE II OF POSTSYNAPTIC
SENSITIVITY IN RAT HIPPOCAMPAL CA1 NEURONS
Aneil M. Shirke, and Roberto Malinow.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, and Department
of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
APStracts 4:133N, 1997.
ABSTRACT
Pre-activated recombinant ?-calcium-calmodulin dependent multifunctional
protein kinase II (CaMKII*) was internally perfused into CA1 hippocampal slice
neurons to test the effect on synaptic transmission and responses to exogenous
application of glutamate analogs. Following measurement of baseline
transmission, internal perfusion of CaMKII* increased synaptic strength in rat
hippocampal neurons and diminished the fraction of synaptic failures.
Following measurement of baseline responses to applied transmitter, CaMKII*
perfusion potentiated responses to kainate but not responses to N-methyl-D-
aspartate (NMDA). Internal perfusion of CaMKII* potentiated the maximal effect
of kainate. Potentiation by CaMKII* did not change the time course of
responses to kainate, while increasing response size by pharmacologically
manipulating desensitization or deactivation rate constants significantly
altered the time course of responses. Nonstationary fluctuation analysis of
responses to kainate showed a decrease in the coefficient of variation (CV)
after potentiation by CaMKII*. These data support the hypothesis that CaMKII
increases postsynaptic responsiveness by increasing the available number of
active ?-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate
channels, and suggests that a similar process may occur during the expression
of long-term potentiation (LTP).
Received 9 April 1997; accepted in final form 9 July 1997.
APS Manuscript Number J286-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 24 July 1997