The Journal of Neuroscience, November 15, 1999, 19(22):9705-9715
Opioid Enhancement of Calcium Oscillations and Burst Events
Involving NMDA Receptors and L-Type Calcium Channels in Cultured
Hippocampal Neurons
Rysard
Przewlocki,
Kathy L.
Parsons,
Dan D.
Sweeney,
Carol
Trotter,
Jeffrey G.
Netzeband,
George R.
Siggins, and
Donna L.
Gruol
Department of Neuropharmacology, The Scripps Research Institute, La
Jolla, California 92037
Opioid receptor agonists are known to alter the activity of
membrane ionic conductances and receptor-activated channels in CNS neurons and, via these mechanisms, to modulate neuronal
excitability and synaptic transmission. In neuronal-like cell lines
opioids also have been reported to induce intracellular
Ca2+ signals and to alter Ca2+
signals evoked by membrane depolarization; these effects on
intracellular Ca2+ may provide an additional
mechanism through which opioids modulate neuronal activity. However,
opioid effects on resting or stimulated intracellular
Ca2+ levels have not been demonstrated in native CNS
neurons. Thus, we investigated opioid effects on intracellular
Ca2+ in cultured rat hippocampal neurons by using
fura-2-based microscopic Ca2+ imaging. The opioid
receptor agonist
D-Ala2-N-Me-Phe4,Gly-ol5-enkephalin
(DAMGO; 1 µM) dramatically increased the amplitude of
spontaneous intracellular Ca2+ oscillations in the
hippocampal neurons, with synchronization of the
Ca2+ oscillations across neurons in a given field.
The effects of DAMGO were blocked by the opioid receptor antagonist
naloxone (1 µM) and were dependent on functional NMDA
receptors and L-type Ca2+ channels. In parallel
whole-cell recordings, DAMGO enhanced spontaneous, synaptically driven
NMDA receptor-mediated burst events, depolarizing responses to
exogenous NMDA and current-evoked Ca2+ spikes. These
results show that the activation of opioid receptors can augment
several components of neuronal Ca2+ signaling
pathways significantly and, as a consequence, enhance intracellular
Ca2+ signals. These results provide evidence of a
novel neuronal mechanism of opioid action on CNS neuronal networks that
may contribute to both short- and long-term effects of opioids.
Key words:
glutamate receptors; synaptic transmission; calcium
channels; NMDA receptors; intracellular calcium; opioid receptors
Copyright © 1999 Society for Neuroscience 0270-6474/99/19229705-11$05.00/0
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