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J Physiol Volume 578, Number 1, 143-157, January 1, 2007 DOI: 10.1113/jphysiol.2006.116178
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CELLULAR

The sigma-1 receptor modulates NMDA receptor synaptic transmission and plasticity via SK channels in rat hippocampus

Marzia Martina1, Marie-Eve B. Turcotte1, Samantha Halman1 and Richard Bergeron1

1 Department of Cellular and Molecular Medicine, Department of Psychiatry, University of Ottawa, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, K1Y 4E9, Canada

The sigma receptor ({sigma}R), 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 {sigma}R-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 {sigma}R-1 agonist, we found that {sigma}R-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 {sigma}R-1 as postsynaptic regulator of synaptic transmission.

(Received 28 June 2006; accepted after revision 25 October 2006; first published online 26 October 2006)
Corresponding author M. Martina: Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, K1Y 4E9, Canada. Email: mmartina{at}ohri.ca




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