The cellular Na+ pump as a site of action for carbon monoxide and glutamate: a mechanism for long-term modulation of cellular activity

Neuron. 1995 Apr;14(4):781-94. doi: 10.1016/0896-6273(95)90222-8.


Carbon monoxide (CO) induces a long-lasting alteration in cerebellar alpha 3-Na,K-ATPase independent of [Na+] but linked to cGMP synthesis and localized to Purkinje neurons. The action of CO is absent in Purkinje neuron-deficient mice, mimicked by 8-Br-cGMP, and blocked by inhibition of PKG. Glutamate (Glu) and metabotropic agonists mimic the action of CO, an effect that requires PKC and is associated with CO synthesis. These data suggest that CO regulates Na,K-ATPase through cGMP and PKG, and that Glu regulates CO through mGluRs. This system is also modulated by NMDA agonists and nitric oxide, possibly via Glu release, as well as by free radicals. These findings offer a mechanism by which CO, Glu, and free radicals can exert specific effects on synaptic transmission (relevant to long-term changes in cell excitability), as well as more general actions on energy metabolism (relevant to the pathophysiology of excitotoxicity).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbon Monoxide / pharmacology*
  • Cerebellum / enzymology
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / metabolism
  • Cyclic GMP / pharmacology
  • Enzyme Activation
  • Free Radicals
  • Glutamic Acid / pharmacology*
  • Homeostasis
  • Mice
  • Nitric Oxide / metabolism
  • Nitric Oxide / pharmacology
  • Protein Kinase C / metabolism
  • Protein Kinases / metabolism
  • Purkinje Cells / enzymology
  • Rats
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / physiology
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Free Radicals
  • Receptors, Metabotropic Glutamate
  • 8-bromocyclic GMP
  • Nitric Oxide
  • Glutamic Acid
  • Carbon Monoxide
  • Protein Kinases
  • Protein Kinase C
  • Sodium-Potassium-Exchanging ATPase
  • Cyclic GMP