title: Contribution of astroglia to functionally activated energy metabolism.
abstract: Studies of local glucose utilization in neural tissues in vivo with the autoradiographic [14C]deoxyglucose method have demonstrated that energy metabolism increases almost linearly with the degree of functional activation, i.e. spike frequency, in the terminal projection zones of activated pathways. The increased metabolism is found in neuropil and is minimal or undetectable in neuronal cell bodies. Electrical stimulation, increased extracellular [K+] ([K+]o), or opening of Na+ channels with veratridine stimulates metabolism in neutral tissues, and this increase is blocked by ouabain, a specific inhibitor of Na+,K(+)-ATPase. Activation of this enzyme to restore ionic gradients across cellular membranes appears to mediate the function-related increase in energy metabolism. The metabolic activation is, therefore, not directly related to the functional activity itself but to processes operating to recover from that activity. The limited spatial resolution of the [14C]DG method precludes identification of cellular elements in neuropil participating in the metabolic activation, e.g. axonal terminals, dendrites, or astrocytic processes enveloping the synapses. We have, therefore, attempted to stimulate in vitro conditions to be expected from functional activation and increased spike activity in vivo, e.g. increased extracellular [K+], intracellular [Na+], or extracellular neurotransmitter levels, and examined their effects on glucose metabolism in neurons and astroglia in culture. Increased [K+]o stimulated [14C]DG phosphorylation in neuronal and mixed neuronal-astroglial cultures, but not in astroglial cultures assayed in bicarbonate buffer; it did occasionally stimulate metabolism in astroglia when assayed in HEPES or phosphate buffers, but these effects were variable and inconsistent. Veratridine (75 microM) stimulated [14C]DG phosphorylation in neurons and astroglia; these stimulations were blocked by 1 mM ouabain or 10 microM tetrodotoxin (TTX), which blocks voltage-dependent Na+ channels. The Na+ ionophore monensin (10 microM) doubled the rate of metabolism, a stimulation that was only partially blocked by ouabain and unaffected by TTX. L-Glutamate (500 microM) stimulated [14C]DG phosphorylation in astroglia, but this stimulation was probably secondary to Na+ uptake into the cells via a sodium/glutamate co-transporter because it was not blocked by inhibitors of NMDA or non-NMDA receptors but was absent in Na(+)-free medium. These results indicate that astroglia contribute to the increased energy metabolism in neuropil during functional activation by mechanisms that promote Na+ entry into the cells.
authors.affiliation: Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Md. 20892-4030, USA.
authors.forename: L
authors.initials: L
authors.lastname: Sokoloff
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: J
authors.initials: J
authors.lastname: Gotoh
authors.forename: B F
authors.initials: BF
authors.lastname: Driscoll
authors.forename: M J
authors.initials: MJ
authors.lastname: Law
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D004734:Energy Metabolism; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D008985:Monensin / Q000494:pharmacology; D009994:Osmolar Concentration; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D051381:Rats / Q000196:embryology; D017207:Rats, Sprague-Dawley; D014701:Veratridine / Q000494:pharmacology
chemical_list: D018698:Glutamic Acid; D014701:Veratridine; D008985:Monensin; D003847:Deoxyglucose; D011188:Potassium