Mechanisms of modulation of AMPA-induced Na+-activated K+ current by mGluR1.
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 Ca(2+) 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 Ca(2+)- and PKC-dependent manner.
Nanou
Evanthia
E
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
El Manira
Abdeljabbar
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007798:Lampreys; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D002614:Chelating Agents; D015221:Potassium Channels; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D004533:Egtazic Acid; D012964:Sodium; D011493:Protein Kinase C; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D011188:Potassium; D002118:Calcium