PT  - JOURNAL ARTICLE
AU  - Rysard Przewlocki
AU  - Kathy L. Parsons
AU  - Dan D. Sweeney
AU  - Carol Trotter
AU  - Jeffrey G. Netzeband
AU  - George R. Siggins
AU  - Donna L. Gruol
TI  - Opioid Enhancement of Calcium Oscillations and Burst Events Involving NMDA Receptors and L-Type Calcium Channels in Cultured Hippocampal Neurons
AID  - 10.1523/JNEUROSCI.19-22-09705.1999
DP  - 1999 Nov 15
TA  - The Journal of Neuroscience
PG  - 9705--9715
VI  - 19
IP  - 22
4099  - http://www.jneurosci.org/content/19/22/9705.short
4100  - http://www.jneurosci.org/content/19/22/9705.full
SO  - J. Neurosci.1999 Nov 15; 19
AB  - 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 agonistd-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.