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 if 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 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.