Influence of Hypoxia on Release and Uptake of Neurotransmitters in Guinea Pig Striatal Slices: Dopamine and Acetylcholine

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We studied the influence of hypoxia on the release of [³H]dopamine ([³H]DA) and [³H] acetylcholine ([³H]ACh), uptake of [³H]DA and [³H]choline and Ca²⁺-influx in guinea pig striatal slices. Tetrodotoxin (TTX)-sensitive and Ca²⁺-dependent electrically evoked release of [³H] DA was not affected by hypoxia, while spontaneous release of [³H] DA was rapidly increased. On the other hand, by hypoxia, the evoked [³H]ACh release gradually decreased and was diminished to about 45% 40 min later. Hypoxia suppressed the V_max of [³H] DA uptake to one third and that of [³H]choline to half of the control values, but with no change in either of the K_m values. Hypoxia reduced both the acetylation and the uptake of [³H]choline in slices preliminarily incubated with 3 mM or 25 mM K⁺ medium. Stimulation-induced Ca²⁺-influx was slightly suppressed and was 78.1% of the control values even after 40 min exposure to hypoxia. The Ca²⁺-dependent neurotransmitter release process itself appears to be well preserved against hypoxia as compared with the uptake process. Our findings imply that hypoxia could result in differential alterations of neural activity depending on the specific sensitivity of the presynaptic process of neurotransmission.