THE CELLULAR NA-MONOXIDE AND GLUTAMATE - A MECHANISM FOR LONG-TERM MODULATION OF CELLULAR-ACTIVITY( PUMP AS A SITE OF ACTION FOR CARBON)

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