TY - JOUR T1 - Kappa-opioid receptor inhibition of calcium oscillations in spinal cord neurons JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.111.071456 SP - mol.111.071456 AU - Lakshmi Kelamangalath AU - Shashank Dravid AU - Joju George AU - Jane Aldrich AU - Thomas Murray Y1 - 2011/03/21 UR - http://molpharm.aspetjournals.org/content/early/2011/03/21/mol.111.071456.abstract N2 - Mouse embryonic spinal cord neurons in culture exhibit spontaneous calcium oscillations from day in vitro (DIV)-6 through DIV-10. Such spontaneous activity in developing spinal cord contributes to maturation of synapses and development of pattern generating circuits. Here we demonstrate that these calcium oscillations are regulated by kappa opioid receptors (KORs). The kappa opioid agonist dynorphin (Dyn)-A (1-13) suppressed calcium oscillations in a concentration-dependent manner and both the nonselective opioid antagonist naloxone and the kappa selective blocker nor-BNI eliminated this effect. The KOR selective agonist U69593 mimicked the effect of Dyn-A (1-13) on calcium oscillations. A kappa specific peptide antagonist, zyklophin, was also able to prevent the suppression of calcium oscillations caused by Dyn-A (1-13). These spontaneous calcium oscillations were blocked by 1 μM tetrodotoxin indicating that they are action potential dependent. Although the L-type voltage gated calcium channel blocker nifedipine did not suppress calcium oscillations, the N-type calcium channel blocker ω-conotoxin inhibited this spontaneous response. Blockers of ionotropic glutamate receptors, NBQX and MK-801, also suppressed calcium oscillations revealing a dependence on glutamate-mediated signaling. Finally, we have demonstrated expression of KORs in glutamatergic spinal neurons and localization in a presynaptic compartment: consistent with previous reports of KOR mediated inhibition of glutamate release. The KOR mediated inhibition of spontaneous calcium oscillations may therefore be a consequence of presynaptic inhibition of glutamate release. ER -