Mechanisms of Modulation of AMPA-Induced Na+-Activated K+ Current by mGluR1

Nanou E, El Manira A. Mechanisms of modulation of AMPA-induced Na+-activated K+ current by mGluR1. J Neurophysiol 103: 441-445, 2010. First published November 4, 2009; doi: 10.1152/jn.00584.2009. Na+-activated K+ (K-Na) channels can be activated by Na+ influx via ionotropic receptors and play a role in shaping synaptic transmission. In expression systems, K-Na channels are modulated by G protein coupled receptors, but such a modulation has not been shown for the native channels. In this study, we examined whether K-Na channels coupled to AMPA receptors are modulated by metabotropic glutamate receptors (mGluRs) in lamprey spinal cord neurons. Activation of mGluR1 strongly inhibited the AMPA-induced K-Na current. However, when intracellular Ca2+ was chelated with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA), the K-Na current was enhanced by mGluR1. Activation of protein kinase C (PKC) mimicked the inhibitory effect of mGluR1 on the K-Na current. Blockade of PKC prevented the mGluR1-induced inhibition of the K-Na current, but did not affect the enhancement of the current seen in BAPTA. Together these results suggest that mGluR1 can differentially modulate AMPA-induced K-Na current in a Ca2+- and PKC-dependent manner.