Endplates after esterase inactivationin vivo: correlation between esterase concentration, functional response and fine structure

Salpeter, Miriam M.; Kasprzak, H.; Feng, Husuan; Fertuck, Helen C.

doi:10.1007/bf01206461

Cited by 78 publications

(32 citation statements)

References 58 publications

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“…In such circumstances, the high level of activity imposed upon fast muscle fibres by their motorneurones might lead to a permanently raised intracellular concentration of calcium. Such high levels of calcium are known to be harmful, perhaps through the activation of proteases (Salpeter, Kasprzak, Feng & Fertuck, 1979;Toth, Karksui, Poberai & Saivay, 1981), and might therefore bring about the eventual disintegration of the muscle fibre. Free calcium has been observed in some muscle fibres from dystrophic patients (Bodensteiner & Engel, 1978) and several workers have shown that the ability ofthe sarcoplasmic reticulum to take up calcium is very much reduced in the muscles of these patients (Samaha & Gergely, 1969;Takagi, Schotland & Rowland, 1973;Peter, Worsfold & Fiehn, 1974).…”

Section: Muscle Reco Ver Y After Nerve Injur Y Mechanism Offibre Damagementioning

confidence: 99%

Different pattern of recovery of fast and slow muscles following nerve injury in the rat.

Lowrie¹,

Vrbová²

1984

The Journal of Physiology

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SUMMARY1. The sciatic nerve was crushed in 5-6-day-old rats and the time course of recovery and changes in physiological and morphological properties of reinnervated fast and slow muscles was compared.2. The maximal tetanic tension developed by the reinnervated muscles was recorded at different times from about 18 days of age, when functional recovery was first seen, until 2 months.3. The maximal indirectly elicited tetanic tension of the reinnervated slow soleus muscle gradually increased from 55 % of normal at 18 days to 75 % of normal at 2 months. In contrast, the tension of the reinnervated fast muscle extensor digitorum longus (e.d.l.) fell sharply from 70 % of normal at 18 days to 40 % at 21 days and remained at that level till the end of the study. 4. The total number of muscle fibres in control, reinnervated and denervated e.d.l. muscles was counted. At 18 days the number of fibres in the reinnervated e.d.l. was similar to normal but by 1 month it had fallen to one-third. This decrease did not take place in permanently denervated muscles until at least 35 days. Loss of fibres in the reinnervated soleus was small.5. During the early stages of reinnervation the contraction and relaxation of the fast muscles was very prolonged. By 1 month the time taken to reach peak twitch tension had decreased to normal values but the relaxation was still slower and remained so for several months.6. The study of fatigue resistance showed that at 18 days the reinnervated fast muscles were as fatigable as normal muscles from animals of the same age. The fatigability of normal muscles increased with age to adult levels, but the reinnervated muscles became more fatigue resistant and remained so.7. Our findings suggest that fast muscles become selectively impaired after nerve injury at 6 days because they lose a large number of fibres after reinnervation.

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Section: Muscle Reco Ver Y After Nerve Injur Y Mechanism Offibre Damagementioning

confidence: 99%

Different pattern of recovery of fast and slow muscles following nerve injury in the rat.

Lowrie¹,

Vrbová²

1984

The Journal of Physiology

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“…At the normal endplate (EP), AChE limits the number of collisions between acetylcholine and the acetylcholine receptor (AChR) and, hence, the duration of the synaptic response (1). Inhibition of the enzyme results in prolonged exposure of AChR to acetylcholine, causing desensitization of AChR (2), a depolarization block at physiologic rates of stimulation (3), and an EP myopathy caused by cationic overloading of the postsynaptic region (4,5).…”

mentioning

confidence: 99%

Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme

Ohno

Brengman

Tsujino

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

244

178

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In skeletal muscle, acetylcholinesterase (AChE) exists in homomeric globular forms of type T catalytic subunits (ACHE T ) and heteromeric asymmetric forms composed of 1, 2, or 3 tetrameric ACHE T attached to a collagenic tail (ColQ). Asymmetric AChE is concentrated at the endplate (EP), where its collagenic tail anchors it into the basal lamina. The ACHE T gene has been cloned in humans; COLQ cDNA has been cloned in Torpedo and rodents but not in humans. In a disabling congenital myasthenic syndrome, EP AChE deficiency (EAD), the normal asymmetric species of AChE are absent from muscle. EAD could stem from a defect that prevents binding of ColQ to ACHE T or the insertion of ColQ into the basal lamina. In six EAD patients, we found no mutations in ACHE T . We therefore cloned human COLQ cDNA, determined the genomic structure and chromosomal localization of COLQ, and then searched for mutations in this gene. We identified six recessive truncation mutations of COLQ in six patients. Coexpression of each COLQ mutant with wild-type ACHE T in SV40-transformed monkey kidney fibroblast (COS) cells reveals that a mutation proximal to the ColQ attachment domain for ACHE T prevents association of ColQ with ACHE T ; mutations distal to the attachment domain generate a mutant Ϸ10.5S species of AChE composed of one ACHE T tetramer and a truncated ColQ strand. The Ϸ10.5S species lack part of the collagen domain and the entire C-terminal domain of ColQ, or they lack only the C-terminal domain, which is required for formation of the triple collagen helix, and this likely prevents their insertion into the basal lamina.

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“…The AChE half-life was then inferred from measurements by comparing the amount of AChE insertion into synapses in entire muscles at various times after initial saturation. These studies suggest that AChEs are very stable in the basal lamina (t1 ⁄ 2 around 20 days) (12,13). In this work, we sought to study AChE dynamics more directly using fluorescence imaging techniques by assaying the intensity of fluorescently-tagged fasciculin 2 at individual junctions in living mice.…”

mentioning

confidence: 99%

Acetylcholinesterase Dynamics at the Neuromuscular Junction of Live Animals

Krejci

Valenzuela

Ameziane

et al. 2006

Journal of Biological Chemistry

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At cholinergic synapses, acetylcholinesterase (AChE) is critical for ensuring normal synaptic transmission. However, little is known about how this enzyme is maintained and regulated in vivo. In this work, we demonstrate that the dissociation of fluorescently-tagged fasciculin 2 (a specific and selective peptide inhibitor of AChE) from AChE is extremely slow. This fluorescent probe was used to study the removal and insertion of AChE at individual synapses of living adult mice. After a one-time blockade of AChEs with fluorescent fasciculin 2, AChEs are removed from synapses initially at a faster rate (t1 ⁄ 2 of ϳ3 days) and later at a slower rate (t1 ⁄ 2 of ϳ12 days). Most of the removed AChEs are replaced by newly inserted AChEs over time. However, when AChEs are continuously blocked with fasciculin 2, the removal rate increases substantially (t1 ⁄ 2 of ϳ12 h), and most of the lost AChEs are not replaced by newly inserted AChE. Furthermore, complete one-time inactivation of AChE activity significantly increases the removal of postsynaptic nicotinic acetylcholine receptors (AChRs). Finally, time lapse imaging reveals that synaptic AChEs and AChRs that are removed from synapses are co-localized in the same pool after being internalized. These results demonstrate a remarkable AChE dynamism and argue for a potential link between AChE function and postsynaptic receptor lifetime.

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Endplates after esterase inactivationin vivo: correlation between esterase concentration, functional response and fine structure

Cited by 78 publications

References 58 publications

Different pattern of recovery of fast and slow muscles following nerve injury in the rat.

Different pattern of recovery of fast and slow muscles following nerve injury in the rat.

Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme

Acetylcholinesterase Dynamics at the Neuromuscular Junction of Live Animals

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