The sigma-1 receptor modulates NMDA receptor synaptic transmission and plasticity via SK channels in rat hippocampus.
The sigma receptor (sigmaR), once considered a subtype of the opioid receptor, is now described as a distinct pharmacological entity. Modulation of N-methyl-D-aspartate receptor (NMDAR) functions by sigmaR-1 ligands is well documented; however, its mechanism is not fully understood. Using patch-clamp whole-cell recordings in CA1 pyramidal cells of rat hippocampus and (+)pentazocine, a high-affinity sigmaR-1 agonist, we found that sigmaR-1 activation potentiates NMDAR responses and long-term potentiation (LTP) by preventing a small conductance Ca2+-activated K+ current (SK channels), known to shunt NMDAR responses, to open. Therefore, the block of SK channels and the resulting increased Ca2+ influx through the NMDAR enhances NMDAR responses and LTP. These results emphasize the importance of the sigmaR-1 as postsynaptic regulator of synaptic transmission.
Martina
Marzia
M
Department of Cellular and Molecular Medicine, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, K1Y 4E9, Canada. mmartina@ohri.ca
Turcotte
Marie-Eve B
ME
Halman
Samantha
S
Bergeron
Richard
R
D000465:Algorithms; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D009292:Narcotic Antagonists / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010423:Pentazocine / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D017480:Receptors, sigma / Q000819:agonists / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D000097605:Sigma-1 Receptor
D001030:Apamin; D002118:Calcium; D009292:Narcotic Antagonists; D010423:Pentazocine; D024681:Potassium Channels, Calcium-Activated; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor