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The Journal of Neuroscience, October 1, 2002, 22(19):8363-8369
Role for P2X Receptors in Long-Term Potentiation
Yuri V.
Pankratov,
Ulyana V.
Lalo, and
Oleg A.
Krishtal
Department of Cellular Membranology, Bogomoletz Institute of
Physiology, 01024 Kiev, Ukraine
ATP receptors participate in synaptic transmission and
intracellular calcium signaling in the hippocampus by providing a
component of the excitatory input to CA1 pyramidal neurons. The
activation of P2X purinoreceptors generates calcium influx that does
not require cell depolarization, but this response desensitizes at increased rates of stimulation. Here we show that inhibition of P2X
receptors dramatically facilitates the induction of long-term potentiation (LTP). High-frequency stimulation (HFS) (1 sec) induced LTP in CA1, whereas brief HFS (0.2 sec) caused only short-term potentiation. However, when P2X receptors were inhibited by PPADS (pyridoxal phosphate-6-azophenyl-2'-4'-disulphonic acid) or
desensitized by the nonhydrolyzable ATP analog  , -methyleneATP,
brief HFS reliably induced LTP. Inhibition of P2X receptors had no
facilitatory effect on LTP when NMDA receptors were blocked. We
hypothesized that P2X receptors affect the threshold for LTP by
altering Ca2+-dependent inactivation of NMDA
receptors. In isolated pyramidal CA1 neurons and hippocampal slices,
activation of P2X receptors did cause inhibition of NMDA
receptor-mediated current. We suggest that, by controlling the
background calcium and thus the activity of NMDA receptors at low
firing frequencies, P2X receptors act as a dynamic low-frequency filter
so that weak stimuli do not induce LTP.
Key words:
P2X receptors; long-term potentiation; NMDA receptor
inactivation; ,-methyleneATP; PPADS; CA1 neurons
Copyright © 2002 Society for Neuroscience 0270-6474/02/22198363-07$05.00/0
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