Amino acid transport in isolated neurons and glia.
Our efforts have been directed towards characterizing amino acid uptake, metabolism and release in bulk-isolated glia and neuronal perikarya studied in parallel with nerve-endings, especially as it concerns the transmitter amino acids and the participation of glia in the clearing of the synpatic space during impulse conduction. A possible neuromodulator role for the glia at the synapse is also suggested by K+-stimulated release. Our most definitive conclusions have been based so far on studies with GABA, although we are also beginning to accumulate data for glutamate related to glutamate-glutamine compartmentation. Glia preferentially accumulate potassium and amino acids compared to neuronal perikarya, have higher Na+/K+-ATPase activity, possess high-affinity, sodium-dependent uptake systems for GABA and glutamate similar to the ones in synaptosomes, and release amino acid in response to a potassium pulse by a calcium-independent process. Low neuronal uptake could be due to loss of dendrites. Unidirectional GABA-flux from the synaptosomal to glial compartment is supported by high GAD in nerve endings compared to high GABA-T in glia. Glutamine may be a transmitter glutamate-precursor in nerve-endings since glutaminase activity is high in nerve-endings, but low in glia where glutamine is presumably made. Glutamine uptake in both glia and synaptosomes obeys low-affinity kinetics in contrast to glutamate, consistent with the inability of glutamine to excite the neuronal membrane. The studies with GABA, which are considerably more extensive, are supported by related work using glia in tissue-culture and autoradiography. There appears to be a suggested difference in the behavior of amines which were poorly taken up by the glial system. Glia, synaptosomes and neuronal perikarya, in general behaved similarly with respect to requirements for uptake and release, except in the case of Ca++, which exerted opposite effects on glial and synaptosomal uptake of GABA. We believe that work along these lines tends to firmly establish a direct role for glial cells as modulators of neuronal excitability and represents a convergence between transmitter amino acid neuropharmacology and cellular biochemistry. This not only deepens and enlarges the vocabulary of synaptic biochemistry but also undoubtedly will have major clinical applications in the fields of epilepsy and behavior.
Amino acid transport in isolated neurons and glia. Our efforts have been directed towards characterizing amino acid uptake, metabolism and release in bulk-isolated glia and neuronal perikarya studied in parallel with nerve-endings, especially as it concerns the transmitter amino acids and the participation of glia in the clearing of the synpatic space during impulse conduction. A possible neuromodulator role for the glia at the synapse is also suggested by K+-stimulated release. Our most definitive conclusions have been based so far on studies with GABA, although we are also beginning to accumulate data for glutamate related to glutamate-glutamine compartmentation. Glia preferentially accumulate potassium and amino acids compared to neuronal perikarya, have higher Na+/K+-ATPase activity, possess high-affinity, sodium-dependent uptake systems for GABA and glutamate similar to the ones in synaptosomes, and release amino acid in response to a potassium pulse by a calcium-independent process. Low neuronal uptake could be due to loss of dendrites. Unidirectional GABA-flux from the synaptosomal to glial compartment is supported by high GAD in nerve endings compared to high GABA-T in glia. Glutamine may be a transmitter glutamate-precursor in nerve-endings since glutaminase activity is high in nerve-endings, but low in glia where glutamine is presumably made. Glutamine uptake in both glia and synaptosomes obeys low-affinity kinetics in contrast to glutamate, consistent with the inability of glutamine to excite the neuronal membrane. The studies with GABA, which are considerably more extensive, are supported by related work using glia in tissue-culture and autoradiography. There appears to be a suggested difference in the behavior of amines which were poorly taken up by the glial system. Glia, synaptosomes and neuronal perikarya, in general behaved similarly with respect to requirements for uptake and release, except in the case of Ca++, which exerted opposite effects on glial and synaptosomal uptake of GABA. We believe that work along these lines tends to firmly establish a direct role for glial cells as modulators of neuronal excitability and represents a convergence between transmitter amino acid neuropharmacology and cellular biochemistry. This not only deepens and enlarges the vocabulary of synaptic biochemistry but also undoubtedly will have major clinical applications in the fields of epilepsy and behavior.