Ca2+-Induced Increase in Oxidative Metabolism of Dissociated Mammalian Brain Neurons: Effect of Extract of Ginkgo Biloba Leaves

Abstract

ABSTRACT-Acetylcholine (ACh) release from the motor nerve terminal in the streptozocin-induced diabetic state was studied in mouse phrenic nerve-diaphragm muscle preparations. Electrically evoked re lease of 3H-ACh from the preparation preloaded with 3H-choline was measured during two consecutive periods of stimulation (S1 and S2). In diabetic mice, the amount of 3H-ACh release during S2 was decreased, and the evoked ACh release declined more steeply with successive stimulation periods than in normal ddY mice. The decrease in release was restored when the presynaptic autoreceptors were stimulated by ac cumulating ACh under the irreversible inhibition of junctional cholinesterase by methanesulfonyl fluoride. This effect was abolished by the administration of (+)-tubocurarine (5 tiM). In diabetic mice, the biphasic (acceleration and suppression) effect by succinylcholine on evoked ACh release was caused at 3 to 10-fold lower concentrations than in normal mice. The degree of enhancement of resting 3H-overflow by suc cinylcholine (10 and 30 ttM) was greater in the diabetic state. These results indicated that in the diabetic state, the decrease in evoked ACh release interferes with its presynaptic action on inducing further release (positive feedback modulation) via the presynaptic nicotinic ACh receptor (n-AChR). The presynaptic hypersensitivity to succinylcholine may be due to the augmentation of presynaptic n-AChR sensitivity caused by the reduction of evoked ACh release in the diabetic state.

Motor unit number estimate as a predictor of motor dysfunction in an animal model of type 1 diabetes

“…These later observations could help explain the reduction in QC seen in our diabetic mice. In accord with our study, Kimura et al (24) found a reduction in stimulus-evoked transmitter release from motor nerve endings of diabetic mice. Furthermore, the sternomastoid muscle of nonobese diabetic mice exhibits an altered distribution of muscle end plate AChRs with the formation of abnormal receptor islands and motor nerve terminal sprouts (28) similar to those we report for the STZ model of diabetes.…”

Skeletal muscle dysfunction in the db/db mouse model of type 2 diabetes

“…11 Evidence for possible transmission failure as a result of reduced synaptic safety factor in diabetes comes from studies showing reduced acetylcholine release in streptozotocin (STZ)-based murine models of diabetes. 22,23 At the same time, however, increased acetylcholine sensitivity has also been shown in STZ-induced diabetes. 24,25 Together with the observation that muscles from both STZ mice and db/db mice show decreased acetylcholinesterase gene expression, 25 this could indicate that the potential impairment of neuromuscular transmission arising from reduced acetylcholine release is compensated, at least to some extent, by mechanisms that increase the postsynaptic effect of the acetylcholine that is actually released.…”

Mechanisms of force loss in diabetic mouse skeletal muscle

“…8 Accordingly, the electrically evoked release of ACh from the phrenic nerve is reduced. 13 Thus, alterations in the structure and function of the ␣-motoneurons may contribute to the decrements in muscle strength in diabetics beyond the losses resulting from reductions in muscle size. It is also possible that changes in the postsynaptic membrane at the NMJ contribute to reduced muscle function in diabetics.…”