Effects of pindolol,sotalol and the optical isomers of propranolol on muscle action potentials and depolarization-secretion coupling in the rat

Muscle action potentials and miniature end-plate potential frequency were studied in different concentrations of pindolol, d-and l-propranolol and sotalol using intracellular microelectrode recording from rat phrenic nerve-diaphragm preparations, d-and l-propranolol at concentrations of 10 to 40 mg/1 and pindolol at 20 to 100 mg/1 slowed down the rate of rise, prolonged rise and half-decay times and reduced the overshoot of the muscle action potentials. Sotalol had similar effects but only at higher concentrations (100 to 200 mg/1). The drugs had no effect on the increase in the miniature end-plate potential frequency obtained with depolarization by increased extracellular potassium concentration.     

Electrophysiological analysis of the effect of cortisone on the neuromuscular apparatus in rats

The action of cortisone on the neuromuscular apparatus was studied in situ in experiments on rats. Combined recordings were made of the action potentials of nerve (AP_n) and muscle (AP_m) and also of intracellular resting membrane potentials (MP) and miniature end-plate potentials (MEPP). Cortisone was injected in a dose of 1.5 mg/100 g body weight daily for 10 days. In the animals receiving the hormone, MP of the muscle fibers was reduced compared with the control, the amplitude of the MEPP was reduced and their frequency increased, the time of neuromuscular transmission was lengthened, and its reliability was reduced (the amplitude of AP_m fell faster in the course of tetanus).Laboratory of Neuromuscular Physiology, Physiological Institute, Leningrad University. Department of General Biology, First Leningrad Medical Institute. (Presented by Academician V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 4, pp. 387–390, April, 1976     

Serotonin modulates neuromuscular transmission in frogs

The effect of 5-hydroxytryptamine (serotonin) on neuromuscular transmission in frog skeletal muscle was studied using voltage clamp technique. Serotonin produced no effect on end-plate currents during low frequency electrical stimulation of the motor nerve, but increased the amplitude depression of multiquantal currents during high-frequency stimulation similar to motor commands fired by motoneurons. It was shown that the inhibitory effect of serotonin on neuromuscular transmission is determined by slow potential-dependent block of open ionic channels in the postsynaptic membrane accumulating during rhythmic activation of the synapse.     

Development of neuromuscular junctions on small mesenteric arteries of the rat

This ultrastructural study has investigated the development of the innervation of second order mesenteric arteries from the ileum region of the rat intestine, particularly, the time course of the formation of the plexus of varicose axons around the arteries, and the formation of autonomic neuromuscular junctions. The time points studied were postnatal days-2, -4, -8 and -13. This study has revealed that the formation of neuromuscular junctions with mature structural characteristics occurred at ~2 weeks postnatal. The plexus of varicose axons developed predominantly between day-4 and day-13, which agrees with previous light microscopy studies of catecholamne containing nerves around similar vessels. At day-2 and day-4, the axons lacked varicosities and were mainly contained in large bundles located in the outer region of the adventitia. The medio-adventitial border consisted of a dense layer of extracellular matrix and fibroblasts. By day-8, there were more axons and most were distributed in smaller bundles. Some had grown through the adventitia to lie at the medio-adventitial border and axon varicosities were also observed. Some varicosities had formed rudimentary neuromuscular contacts. By day-13, there were significantly more contacting varicosities compared to day-8. They were structurally more mature, being twice the size with three times the number of synaptic vesicles and consistently contained a mitochondrion. Conversely, the neuromuscular contact areas were similar at both time points. Some organisation of the synaptic vesicles associated with the prejunctional membrane, was evident in varicosities at day-8 but there were no presynaptic membrane specialisations similar to the putative neurotransmitter release sites found at mature skeletal neuromuscular junctions. The aggregation of small vesicles at the prejunctional membrane was more pronounced in neuromuscular junctions at day-13 with some having presynaptic membrane specialisations. Comparison of the structure of developing autonomic neuromuscular junctions with that of skeletal neuromuscular junctions has revealed a number of similarities.     

Desensitization of the post-synaptic membrane of neuromuscular synapses induced by spontaneous quantum secretion of mediator

Experiments on isolated frog neuromuscular junctions in voltage-clamped conditions demonstrated increases in the probability of spontaneous release of quanta of mediator, resulting in increases in the K⁺ ion concentration in the perfusion solution, and changes in the endplate miniature current amplitude induced by increased quantum generation were studied. Factors promoting the desensitization of the post-synaptic cholinergic membrane (inhibition of acetylcholinesterase and addition of proadifen) to levels greater than a certain (critical) frequency of endplate miniature current of the order of 50 spikes/sec were found to result in accumulation of activity and progressive reductions in the sensitivity of the post-synaptic membrane to the mediator acetylcholine. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 3. pp. 67–72, March, 1997.     

放散式体外冲击波对神经肌肉接头影响的研究进展

神经肌肉接头（NMJ）是运动神经元轴突末梢和相应肌纤维间连接的效应位点,是动作电位产生的基础,而NMJ处的乙酰胆碱受体等物质对于动作电位传导具有重要意义。痉挛患者上运动神经元受损时,周围神经持续地通过NMJ向肌肉发放冲动,肌肉出现持续性收缩。研究显示放散式体外冲击波对NMJ有一定作用,可减少动作电位的产生,有助于痉挛的缓解,但冲击波在NMJ处的具体作用机制尚不完全明确,仍需进一步探明。     

Possible involvement of neurokinin receptors in CNS and neuromuscular synapse in the realization of the effects of CAPAH and substance P

Nootropic non-anticholinesterase organophosphorus preparation CAPAH and substance P produced similar and dose-dependent effects on the amplitude and temporal parameters of miniature endplate potentials in mammalian neuromuscular synapse. Neurokinin receptor antagonist Win-51.708 abolished the effects of these agents. In behavioral experiments substance P moderated the mnemotropic and antidepressant effects of CAPAH. It was assumed that neurokinin receptors are the targets of CAPAH and substance P in CNS and neuromuscular synapse.     

Increased asynchronous release and aberrant calcium channel activation in amyloid precursor protein deficient neuromuscular synapses

Despite the critical roles of the amyloid precursor protein (APP) in Alzheimer's disease pathogenesis, its physiological function remains poorly established. Our previous studies implicated a structural and functional activity of the APP family of proteins in the developing neuromuscular junction (NMJ). Here we performed comprehensive analyses of neurotransmission in mature neuromuscular synapse of APP deficient mice. We found that APP deletion led to reduced paired-pulse facilitation and increased depression of synaptic transmission with repetitive stimulation. Readily releasable pool size and total releasable vesicles were not affected, but probability of release was significantly increased. Strikingly, the amount of asynchronous release, a measure sensitive to presynaptic calcium concentration, was dramatically increased, and pharmacological studies revealed that it was attributed to aberrant activation of N- and L-type Ca(2+) channels. We propose that APP modulates synaptic transmission at the NMJ by ensuring proper Ca(2+) channel function.     

Corticosteroids and neuromuscular transmission: Electrophysiological investigation of the effects of prednisolone on normal and anticholinesterase-treated neuromuscular junction

The effect of prednisolone on indirectly stimulated rat muscle twitch was investigated at normal and prostigmine-treated neuromuscular junctions. In vivo, predenisolone up to 150 mg/kg body weight did not affect twitch contraction in normal animals. In neostigmine-pretreated animals, however, doses between 12.5 and 90 mg/kg could entirely abolish the anticholinesterase-induced twitch augmentation. In vitro, prednisolone produced a depressant effect on the twitch of a normal phrenic nerve diaphragm preparation which could amount to 20%. When the preparation was pretreated with neostigmine the augmented twitch could be depressed by 10^–3 to 10^–6 mol/l prednisolone to levels below the untreated control. Part of this effect is owing to a suppression of the neostigmine-induced, stimulus-bound repetitive firing of the motor nerve terminals, but to explain the full effect a further inhibitory action on neuromuscular transmission must be assumed. The latter could be accounted for by a depolarizing interaction of prednisolone and neostigmine on the nerve terminals resulting in conduction block. An action of prednisolone on postsynaptic receptors could also be considered. Such effects of the glucocorticoid might contribute to the exacerbation of muscular weakness occasionally observed in patients with myasthenia gravis at the beginning of steroid therapy.     

Effect of armin on the ultrastructure of the neuromuscular synapse

Changes in the ultrastructure of motor endings under the influence of the cholinesterase inhibitor armin (5·10^–7 g/ml) at rest and during electrical stimulation of the nerve were studied in preparations of the rat phrenic nerve and diaphragm. At rest, armin was found to cause ultrastructural disturbances of the endings similar to those arising in the control during nerve stimulation. Electrical stimulation in the presence of armin caused no further changes in the ultrastructure of the neuromuscular junction. The results indicate the important role of disturbances of the function of the presynaptic apparatus in the mechanisms of the blocking action of armin on neuromuscular conduction.Leningrad. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 95–99, July, 1979.     

Effect of exogenous acetylcholine on neuromuscular transmission in the stimulated rat diaphragm

Nerve stimulation is performed in rat phrenicodiaphragmal preparations with armine-inhibited acetylcholinesterase. Acetylcholine (1×10⁻⁷ M) is added to the saline for 15 min, and as it is washed off (during 1–2 h), the amplitude of isometric contractions and of the total action potential increases in the continuously stimulated muscle. Contractions in response to direct muscle stimulation remain unchanged. The membrane resting potential of muscle fibers exposed to acetylcholine shifts by 2–3 mV toward hyperpolarization and remains at this level for 2 h after the removal of acetylcholine from the saline. Presented by S. N. Golikov, Member of the Russian Academy of Medical Sciences Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 11, pp. 457–459, November, 1994     

Diagnostic immunohistochemistry in neuromuscular disorders

Most neuromuscular disorders display only non-specific myopathological features in routine histological preparations. However, a number of proteins, including sarcolemmal, sarcomeric, and nuclear proteins as well as enzymes with defects responsible for neuromuscular disorders, have been identified during the past two decades, allowing a more specific and firm diagnosis of muscle diseases. Identification of protein defects relies predominantly on immunohistochemical preparations and on Western blot analysis. While immunohistochemistry is very useful in identifying abnormal expression of primary protein abnormalities in recessive conditions, it is less helpful in detecting primary defects in dominantly inherited disorders. Abnormal immunohistochemical expression patterns can be confirmed by Western blot analysis which may also be informative in dominant disorders, although its role has yet to be established. Besides identification of specific protein defects, immunohistochemistry is also helpful in the differentiation of inflammatory myopathies by subtyping cellular infiltrates and demonstrating up-regulation of subtle immunological parameters such as cell adhesion molecules. The role of immunohistochemistry in denervating disorders, however, remains controversial in the absence of a reliable marker of muscle fibre denervation. Nevertheless, as well as the diagnostic value of immunocytochemical analysis it may also widen understanding of muscle fibre pathology as well as help in the development of therapeutic strategies.     

State of neuromuscular transmission in rats with experimental hypoparathyroidism

A disturbance of neuromuscular transmission, characterized by a decrease in the threshold strength of indirect stimulation, a decrease in the amplitude of the combined action potential of the muscle, a shortening of the latent period and of the absolute and relative refractory phases, and changes in the character of the response of the muscle to indirect repetitive stimulation was found in experiments on albino rats with experimental hypoparathyroidism. After intravenous injection of neostigmine into the experimental animals the various indices showed a tendency to return to their values in the control experiments. It is concluded that the disturbance of neuromuscular transmission is connected with a presynaptic defect and that it may be of definite importance in the development of the motor disturbances observable in hypoparathyroidism.Central Research Laboratory, Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 6, pp. 654–656, June, 1977     

Electromyographic biofeedback: Behavioral treatment of neuromuscular disorders

Electromyographic biofeedback is becoming widely used to help patients regain voluntary control of specific muscles affected by neuromuscular disorders. Electromyographic feedback training has been employed in the rehabilitation of patients affected by poliomyelitis, cerebrovascular accident, torticollis, nerve injury, temporomandibular joint syndrome, bruxism, and other disorders. While EMG biofeedback appears to be a promising treatment technique, the research literature on its effectiveness consists mainly of uncontrolled case reports and clinical trials. It is concluded that new studies with more sophisticated designs and more careful control are needed to demonstrate that EMG biofeedback makes a unique contribution to the treatment of neuromuscular disorders. Research is needed to identify relevant patient characteristics predictive of success, specify appropriate muscle groups for the treatment of particular disorders, determine how feedback can be most efficiently combined with more conventional techniques in achieving a therapeutic effect, and establish meaningful criteria of success in the treatment of neuromuscular disorders.The preparation of this article was supported by NIMH Grant 8881-2 to Elliot Mishler and NIMH Grant 1-R01 MH 24103 to Richard S. Surwit.