Synaptosomal calcium metabolism during hypoxia and 3,4-diaminopyridine treatment.
A decline in the calcium-dependent release of neurotransmitters appears to underlie the decreased neuronal function that accompanies reduced oxygen tensions (hypoxia). To determine if alterations in calcium uptake are primary to these changes, synaptosomal calcium uptake was measured in the presence of 100%, 2.5%, or 0% oxygen. Calcium uptake declined 60.2 +/- 0.1 and 82.4 +/- 2.5% with 2.5% and 0% when compared with 100% oxygen, respectively. 3,4-Diaminopyridine stimulated calcium uptake by synaptosomes when they were incubated in low-potassium media. It also diminished the hypoxic-induced decline in calcium uptake to 30.6 +/- 3.1 and 33.5 +/- 3.1% with 2.5% and 0% oxygen, respectively. External binding to the synaptosomal plasma membrane declined to 29.2 +/- 0.3 or 11.8 +/- 0.9% when the oxygen tension was reduced to 2.5% or 0% oxygen. 3,4-Diaminopyridine increased this superficial binding from 111.7 +/- 0.3 to 86.5 +/- 0.9 or 23.4 +/- 0.9% with 100%, 2.5%, or 0% oxygen when compared with 100% oxygen without 3,4-diaminopyridine, respectively. Thus, the decline in neuronal processing that accompanies acute hypoxia may be due to altered calcium homeostasis, which diminishes neurotransmitter release.
D015761:4-Aminopyridine / Q000031:analogs & derivatives*; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D051379:Mice; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000631:Aminopyridines; D015761:4-Aminopyridine; D000077770:Amifampridine; D002118:Calcium