Abstract
Resting non-quantal acetylcholine (ACh) and probably glutamate (Glu) release from nerve endings activates M1- and NMDA receptor-mediated Ca2+ entry into the sarcoplasm with following activation of NOS and production of NO. This is a trophic message from motoneurons, which keeps the Cl− transport inactive in the innervated sarcolemma. After denervation, the secretion of ACh and Glu at the neuromuscular junction is eliminated within 3–4 h and the production of NO in the sarcoplasm is lowered. As a result, the Cl− influx is probably activated by dephosphorylation of the Cl− transporter with subsequent elevation of intracellular Cl− concentration. The equilibrium Cl− potential becomes more positive and the muscle membrane becomes depolarized.
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REFERENCES
Albuquerque, E. X., Schuh, F. T., and Kauffman, F. C. 1971. Early membrane depolarization of the fast mammalian muscle after denervation. Pflugers Arch. 328:36–50.
Shabunova, I. and Vyskočil, F. 1982. Postdenervation changes of intracellular potassium and sodium measured by ion selective microelectrodes in rat soleus and extensor digitorum longus muscle fibers. Pfluegers Arch. 394:161–164.
Lorkovic, H. and Tomanek, R. J. 1977. Potassium and chloride conductances in normal and denervated rat muscles. Am. J. Physiol. 232:C109–C114.
Bray, J. J., Hawken, M. J., Hubbard, J. I., Pockett, S., and Wilson, L. 1976. The membrane potential of rat diaphragm muscle fibers and the effect of denervation. J. Physiol. 255:651–667.
Urazaev, A. Kh., Chikin, A. V., Volkov, E. M., Poletaev, G. I., and Khamitov, Kh. S. 1987. Effect of acetylcholine and carbachol on the resting membrane potential in diaphragm muscle of the rat after denervation [in Russian]. Sechenov's Physiol. J. 40:360–362.
Urazaev, A. Kh., Naumenko, N. V., Poletayev, G. I., and Nikolsky, E. E., F. 1998. The effect of glutamate and inhibitors of NMDA receptors on postdenervation decrease of membrane potential in rat diaphragm. Mol. Chem. Neuropathol. 33:163–174.
Urazaev, A. Kh., Naumenko, N. V., Nikolsky, E. E., and Vyskočil, F. 1999. The glutamate and carbachol effects on the early post-denervation depolarization in rat diaphragm are directed towards furosemide-sensitive chloride transport. Neurosci. Res. 33:81–86
Urazaev, A. Kh., T., Poletaev, G. I., Nikolsky, E. E., and Vyskočil, F. 1995. Muscle NMDA receptors regulate the resting membrane potential through NO-synthase. Physiol. Res. 44:205–208.
Urazaev, A. Kh., Naumenko, N. V., Poletayev, G. I., Nikolsky, E. E., and Vyskočil, F. 1996. Nitroprusside decrease the early postdenervation depolarization of diaphragm muscle fibers of the rat. Eur. J. Pharmacol. 316:219–222.
Urazaev, A. Kh., Naumenko, N. V., Poletayev, G. I., Nikolsky, E. E., and Vyskočil, F. 1997. Acetylcholine and carbachol prevent muscle depolarization in denervated rat diaphragm. NeuroReport 8:403–406.
Urazaev, A. Kh., Naumenko, N. V., Malomough, A., Nikolsky, E. E., and Vyskočil, F. 2000. Carbachol and acetylcholine delay the early postdenervation depolarization of muscle fibers through M1-cholinergic receptors. 2000. Neurosci. Res. 37:255–263.
Urazaev, A. Kh., Surovtsev, V. A., Chikin, A. V., Volkov, E. M., Poletaev, G. I., and Khamitov, Kh. S. 1987. Neurotrophic control of transmembrane Cl--pump in mammalian muscle fibers [in Russian]. Neurophysiology, 19:766–771.
Betz, W. J., Caldwell, J. H., and Harris, G. L. 1986. Effect of denervation on a steady electric current generated at the end-plate region of rat skeletal muscle. J. Physiol. 373:97–114.
Sitdikov, R. F., Urazaev, A., Volkov, E. M., Poletaev, G. I., and Khamitov, Kh. S., 1991. Neurotrophic control of the ionic regulation mechanisms for intracellular water content in muscle fibers of mammals [in Russian]. Neirofiziologiia 23:625–628.
Chikin, A. V., Urazaev, A., Volkov, E. M., Poletaev, G. I., and Khamitov, Kh. S. 1987. Effect of disruption of chloride conductance on the development of denervation changes in muscle fiber membranes of the rat [in Russian]. Fiziol. Zh. SSSR 73:51–55.
Malomouzh, A. I., Mukhtarov, M. R., Nikolsky, E. E., Vyskočil, F., Lieberman, E. M., and Urazaev, A. Kh. 2003. Glutamate regulation of non-quantal release of acetylcholine in the rat neuromuscular junction. J. Neurochem. in press.
Stamler, J. S. and Meissner, G. 2001. Physiology of nitric oxide in skeletal muscle. Physiol. Rev. 81:209–237.
Grozdanovic, Z. 2001. NO message from muscle. Microscop. Res. Technique 55:148–153.
Gutmann, E. 1976. Neurotrophic relations. Annu. Rev. Physiol. 38:177–216.
McArdle, J. J. 1983. Molecular aspects of the trophic influence of nerve on muscle. Prog. Neurobiol. 21:135–138.
Nikolsky, E. E., Voronin, V. A., and Oranska, T. I. 1985. Dynamics of quantal and nonquantal acetylcholine release after motor nerve cutting [in Russian]. Dokladi Akademii Nauk SSSR, 281:762–764.
Zemková, H., Vyskočil, F., and Edwards C. 1987. A study on early postdenervation changes of nonquantal and quantal acetylcholine release in the rat diaphragm. Pflueg. Arch. 409:540–546.
Vyskočil, F., Nikolsky, E. E., Zemková H., and Krušek, J. 1995. The role of nonquantal release of acetylcholine in regulation of postsynaptic membrane electrogenesis. J. Physiol. (Paris) 89:157–162.
Katz, B. and Miledi, R. 1977. Transmitter leakage from motor nerve endings. Proc. Royal Soc. Lond. Ser. B 196:59–72.
Vyskočil, F. and Illes, P. 1977. Nonquantal release of transmitter at mouse neuromuscular junction and its dependence on the activity of Na-K-ATPase. Pflueger. Arch. 370:295–297.
Edwards, C., Doležal, V., Tuček, S., Zemková, H., and Vyskočil, F. 1985. Is an acetylcholine transport system responsible for nonquantal release of acetylcholine at the rodent myoneural junction? Proc. Natl. Acad. Sci. USA 82:3514–3518.
Vizi, E. S. and Vyskočil, F. 1979. Changes in total and quantal release of acetylcholine in the mouse diaphragm during activation and inhibition of membrane ATPase. J. Physiol. 286:1–14.
Doležal, V. and Tuček, S. 1983. The synthesis and release of acetylcholine in normal and denervated rat diaphragms during incubation in vitro. J. Physiol. 334:461–474.
Nikolsky, E. E., Oranska, T. I., and Vyskočil, F. 1996. Non-quantal acetylcholine release in the mouse diaphragm after phrenic nerve crush and during recovery. Exp. Physiol. 81:341–348.
Sitdikov, R. F., Urazaev, A., Volkov, E. M., Poletaev, G. I., and Khamitov Kh. S. 1989. Effects of hyperosmolarity and furosemide on resting membrane potentials and skeletal muscle fiber volume in rats [in Russian]. Bull. Eksp. Biol. Med. 108:563–566.
Vyskočil, F., Nikolsky, E. E., and Edwards, C. 1983. An analysis of the mechanisms underlying the nonquantal release of acetylcholine at the mouse neuromuscular junction. J. Neurosci. 9:429–435.
Dlouhá, H., Teisinger, J., and Vyskočil, F., 1979. Activation of membrane Na+/K+-ATPase of mouse skeletal muscle by acetylcholine and its inhibition by alpha-bungarotoxin, curare and atropine. Pflügers Arch. 380:101–104.
Nikolsky, E. E., Zemková, H., Voronin, V. A., and Vyskočil, F. 1994. Participation of nonquantal acetylcholine in release in surplus polarization of the mouse diaphragm fibers at the end-plate zone. J. Physiol. 477:497–502.
Vyskočil, F. and Gutmann, E. 1977. Anabolic effect of testosterone on the levator ani muscle of the rat. Pflügers Arch. 371:3–8.
Vincent, S. R. and Hope B. T. 1992. Neurons that say NO. Trends Neurosci. 15:108–113.
Mukhtarov, M. R., Vyskočil, F., Urazaev, A. K., and Nikolsky, E. E. 1999. Nonquantal acetylcholine release is increased after nitric oxide synthase inhibition. Physiol. Res. 48:315–317.
Mukhtarov, M. R., Urazaev, A. K., Nikolsky, E. E., and Vyskocil, F. 2000. Effect of nitric oxide and NO synthase inhibition on nonquantal acetylcholine release in the rat diaphragm. Eur. J. Neurosci. 12:980–986.
Hosey, M. M. 1992. Diversity of structure, signaling and regulation within the family of muscarinic cholinergic receptors. FASEB J. 6:845–852.
Reyes, R. and Jaimovich, E. 1996. Functional muscarinic receptors in cultured skeletal muscle. Arch. Biochem. Biophys. 331:41–47.
Vizi, E. S. and Somogyi, G. T. 1989. Prejunctional modulation of acetylcholine release from the skeletal neuromuscular junction: Link between positive (nicotinic)-and negative (muscarinic)-feedback modulation. Brit. J. Pharmacol. 97:65–70.
Nikolsky, E. E., Bukharaeva, E. A., Strunsky, E. G., and Vyskočil, F. 1991. Depression of miniature endplate potential frequency by acetylcholine and its analogues in frog. Brit. J. Pharmacol. 104:1024–1032.
Wessler, I. 1989. Control of transmitter release from the motor nerve by presynaptic nicotinic and muscarinic autoreceptors. Trends Pharmacol. Sci. 10:110–114.
Wessler, I. 1989. Acetylcholine at motor nerves: Storage, release, and presynaptic modulation by autoreceptors and adrenoceptors. Int. Rev. Neurobiol. 34:283–384.
Zemková, H., Vyskočil, F., and Edwards, C. 1990. The effects of nerve terminal activity on nonquantal release of acetylcholine at the mouse neuromuscular junction. J. Physiol. 423:631–640.
Meister, B., Arvidsson, U., Zhang, X., Jacobsson, G., Villar, M. J., and Hokfelt, T. 1993. Glutamate transporter mRNA and glutamate-like immunoreactivity in spinal motoneurons. Neuroreport 5:337–340.
Kerkut, G. A., Shapiro, A., and Walker, R. J. 1967. The transport of C-labelled material from CNS to muscle along a nerve trunk. Comp. Biochem. Physiol. 23:729–748.
Waerhaug, O. and Ottersen, O. P. 1993. Demonstration of glutamate-like immunoreactivity at rat neuromuscular junctions by quantitative electron microscopic immunocytochemistry. Anat. Embryol. (Berl.) 188:501–513.
Berger, U. V., Carter, R. E., and Coyle, J. T. 1995. The immunocytochemical localization of N-acetylaspartyl glutamate, its hydrolysing enzyme NAALADase, and the NMDAR-1 receptor at a vertebrate neuromuscular junction. Neuroscience 64:847–850.
Davies, J. and Watkins, J. C. 1982. Actions of D and L forms of 2-amino-5-phosphonovalerate and 2-amino-4-phosphonobutyrate in the cat spinal cord. Brain Res. 235:378–386.
Mayer, M. L., Vyklicky, L. J., and Westbrook, G. L. 1989. Modulation of excitatory amino acid receptors by group II B metal cations in cultured mouse hippocampal neurons. J. Physiol. 415:329–350.
Westbrook, G. L. and Mayer, M. L. 1987. Micromolar concentration of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons. Nature 328:640–643.
Legendre, P. and Westbrook, G. L. 1990. The inhibition of single N-methyl-D-aspartate-activated channels by zinc ions on cultured rat neurons. J. Physiol. 429:429–449.
Wong, E. H. F., Kemp, J. A., Priestly, T., Knight, A. R., Woodruff, G. N., and Iversen, L. L. 1986. The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc. Natl. Acad. Sci. USA 83:7104–7108.
Schneggenburger, R., Zhou, Z., Konnerth, A., and Neher, E. 1993. Fractional contribution of calcium to the cation current through the glutamate receptor channels. Neuron 11:133–143.
Stankovičová, T., Zemková, H., Breier, A., Amler, E., Burkhard, M., and Vyskočil, F. 1995. The effect of calcium and calcium channel blockers on sodium pump. Pfluegers Arch. Eur. J. Physiol. 429:716–721.
Peters, S., Koh, J., and Choi, D. W. 1987. Zinc selectively blocks the action of N-methyl-D-aspartate on cortical neurons. Science 236:589–593.
Jahr, C. E. and Stevens, C. F. 1990. Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics. J. Neurosci. 10:3178–3182.
Hahn, J. S., Aizenmann, E., and Lipton, S. A. 1988. Central mammalian neurons normally resistant to glutamate toxicity are made sensitive by elevated extracellular Ca2+: Toxicity is blocked by the N-methyl-D-aspartate antagonist MK-801. Proc. Natl. Acad. Sci. USA 85:6556–6560.
Amador, M. and Dani, J. A. 1991. MK-801 inhibition of nicotinic acetylcholine receptor channels. Synapse 7:207–215.
Howell, G. A., Welch, M. G., and Frederickson, C. J. 1984. Stimulation-induced uptake and release of zinc in hippocampal slices. Nature 308:736–738.
Assaf, S. Y. and Chung, S.-H. 1984. Release of endogenous Zn2+ from brain tissue during activity. Nature 308:734–736.
Masters, B. A., Quaife, C. J., Erickson, J. C., Kelly, E. J., Froelick, G. L., Zambrowicz, B. P., Brinster, R. L., and Palmiter, R. D. 1994. Metallothionein III is expressed in neurons that sequester zinc in synaptic vesicles. J. Neurosci. 14:5844–5857.
Johnson, J. W. and Ascher, P. 1987. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529–531.
Wood, E. R., Bussey, T. J., and Philips, A. G. 1994. A glycine antagonist 7-chlorkynuretic acid attenuates ischemia-induced learning deficits. Neuroreport 4:151–154.
Moncada, S., Palmer, R. M. J., and Higgs, E. A. 1991. Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol. Rev. 43:1709–1715.
Bohme, G. A., Bon, C., Stutzmann, J. M., Doble, A., and Blanchard, J. 1991. Possible involvement of nitric oxide in long-term potentiation, Eur. J. Pharmacol. 199:379–381.
Antonov, S. M. and Magazanik, L. G. 1988. Intense nonquantal release of glutamate in an insect neuromuscular junction. Neurosci. Lett. 93:204–208.
Kobzik, L., Reid, M. B., Bredt, D. S., and Stamler, J. S. 1994. Nitric oxide in skeletal muscle. Nature, 372:545–548.
Kilpatrick, E. V. and Cocks, T. M. 1994. Evidence for differential roles of nitric oxide (NO) and hyperpolarization in endothelium-dependent relaxation of pig isolated coronary artery. Br. J. Pharmacol. 112:557–565.
Miyoshi, H. and Nakaya, Y. 1994. Endotoxin-induced non-endothelial nitric oxide activates the Ca(2+)-activated K+ channel in cultured vascular smooth muscle cells. J. Mol. Cell Cardiol. 26:1487–1495.
Böhme, G. A, Bon, C., Stutzmann, J. M., Doble, A., and Blanchard, J. C. 1991. Possible involvement of nitric oxide in long-term potentiation. Eur. J. Pharmacol. 199:379–381.
Poletaev G. I. 1970. Mechanism of imidazole action on frog neuromuscular junctions [in Russia]. Sechenov's Physiol. J. 56:64–67.
Kohen, R., Yamamoto, Y., Cundy, K. C., and Ames, B. N. 1988. Antioxidant activity of carnosine homocarnosine and anserine present in muscle and brain. PNAS 85:3175–3179
Ciani, S. and Edwards, C. 1963. The effect of acetylcholine on neuromuscular transmission in the frog. Pharmacol. Exp. Ther. 142:21–29.
Bray, J. J., Forrest, J. W., and Hubbard, J. I. 1982. Evidence for the role of nonquantal acetylcholine in the maintenance of the membrane potential of rat skeletal muscle. J. Physiol. F326:285–296.
Grozdanovich, Z. and Grossrau, R. 1998. Co-localization of nitric oxide synthase I (NOS I) and NMDA receptor subunit 1 (NMDAR-1) at the neuromuscular junction in rat and mouse skeletal muscle. Cell Tissue Res. 291:57–63.
Mukhtarov, M. R., Urazaev, A. K., Nikolski, E. E., and Vyskočcil, F. 2001. Modulation by nitric oxide (NO) of the intensity of nonquantal mediator secretion in neuromuscular junctions in rats. Neurosci. Behav. Physiol. 31:451–455.
Galkin, A. V., Giniatullin, R. A., Mukhtarov, M. R., Švandová, I., Grishin, S. N., and Vyskočil, F. 2001. ATP but not adenosine inhibits nonquantal acetylcholine release at the mouse neuromuscular junction. Eur. J. Neurosci. 13:2047–2053.
Dulhunty, A. F. 1978. The dependence of membrane potential on extracellular chloride concentrations in mammalian muscle fibers. J. Physiol. 276:67–82.
Tews, D. S. 2001. Role of nitric oxide and nitric oxide synthases in experimental models of denervation and reinnervation. Microsc. Res. Tech. 55:181–186.
Švandová, I., Vyskočil, F., and Ujec, E. 2001. Nitric oxide synthase inhibition partially imitates postdenervation tetrodotoxin resistance and anodal break excitation in innervated rat muscles. Physiol. Res. 50:P29.
Melzer, W., Schneider, M. F., Simon, B. J., and Szucs, G. 1986. Intramembrane charge movement and calcium release in frog skeletal muscle. J. Physiol. 373:481–511.
Bray, J. J. and Harris, A. J. 1975. Dissociation between nerve-muscle transmission and nerve trophic effects on rat diaphragm using type D botulinum toxin. J. Physiol. 253:53–77.
Adámek, S., Schutzner, J., Seidle, Z, Smat, V., Pit`ha, J. 1996. Correlation of computer tomography findings with surgical findings in patients with myasthenia gravis. Rozhl. Chir. 75:237–239.
Schutzner, J., Smat, V., Patko, P., Adámek, S., Sláma, J. 1999. Surgical therapy of thymomas. Sb. Lek. 100:27–31.
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Vyskočil, F. Early Postdenervation Depolarization Is Controlled by Acetylcholine and Glutamate via Nitric Oxide Regulation of the Chloride Transporter. Neurochem Res 28, 575–585 (2003). https://doi.org/10.1023/A:1022833709448
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DOI: https://doi.org/10.1023/A:1022833709448