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Published on: September 4, 2015
The sigma-1 receptor modulates NMDA receptor synaptic transmission and plasticity via SK channels in rat hippocampus
Marzia Martina1, Marie-Eve B Turcotte, Samantha Halman
1Department of Cellular and Molecular Medicine, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, K1Y 4E9, Canada. mmartina@ohri.ca
Abstract:
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.
