Binding of Choline Acetyltransferase in the Nerve Ending Particles of Brain

Abstract

THE highest concentration of choline acetyltransferase (ChAc) is found in the crude mitochondrial fraction of brain homogenates¹ in non-mitochondrial particles² from isolated nerve endings³. The nerve ending particles obtained by subcellular fractionation of the brain contain a number of synaptic vesicles (or tubules⁴) and there is little doubt that most of the acetylcholine of the nerve endings is contained in these structures^5–7. The localization and binding of ChAc in the nerve ending particles are much more debatable. The enzyme remains firmly attached to the nerve ending particles even when these are washed repeatedly. Treatment with ether or certain other agents is necessary in order to observe its full activity; but even after this treatment the enzyme still remains bound to the particles¹, whereas acetylcholine is fully released². On the other hand, Whittaker, Michaelson and Kirkland⁸ found that, after exposure to hypo-osmotic conditions, most of the ChAc dissolved, while most of the acetylcholine remained bound to the particles. In their experiments, hypo-osmotic treatment of crude mitochondrial fractions of whole guinea-pig brains caused the release of most of the ChAc, lactate dehydrogenase and potassium ions, all three being released in very nearly the same proportion. This led them to conclude that ChAc is freely dissolved in the cytoplasm within the nerve endings.