Expression of acetylcholine receptor isoforms at extraocular muscle endplates.

PURPOSE To determine the expression of fetal and adult acetylcholine receptor (AChR) isoforms among extraocular muscle (EOM) en plaque and en grappe endplates. METHODS Antibodies against peptide fragments of the gamma- and epsilon-subunits of the fetal and adult AChRs and alpha-bungarotoxin were used in immunofluorescence experiments to stain rat neonatal leg, adult diaphragm, and extraocular rectus muscle endplates. RESULTS Anti-epsilon antibodies intensely stained diaphragm endplates weakly stained rare neonatal endplates. Anti-gamma antibodies stained neonatal, but not diaphragm, endplates. Anti-epsilon antibodies bound to all en plaque and en grappe endplates of extraocular muscle. Anti-gamma antibodies bound to global and orbital en grappe endplates. All en plaque endplates of the orbital region and a subset of endplates in the global region stained with anti-gamma antibodies. CONCLUSIONS All en grappe endplates and certain en plaque endplates of EOM are the only mature endplates that coexpress the adult and fetal AChR isoforms. The expression of both isoforms may be important to determine contractile properties, protein expression regulation, and EOM susceptibility to myasthenia gravis.

[1]  R. Ruff,et al.  The gamma-Subunit of the Acetylcholine Receptor Is Not Expressed in the Levator Palpebrae Superioris , 1995, Neurology.

[2]  R. Ruff,et al.  Insights into Possible Skeletal Muscle Nicotinic Acetylcholine Receptor (AChR) Changes in Some Congenital Myasthenias from Physiological Studies, Point Mutations, and Subunit Substitutions of the AChR a , 1993, Annals of the New York Academy of Sciences.

[3]  R. Horton,et al.  The 'embryonic' gamma subunit of the nicotinic acetylcholine receptor is expressed in adult extraocular muscle , 1993, Neurology.

[4]  J. Sanes,et al.  Synaptic structure and development: The neuromuscular junction , 1993, Cell.

[5]  R. Ruff,et al.  Ca sensitivity and acetylcholine receptor currents of twitch and tonic snake muscle fibers. , 1990, The American journal of physiology.

[6]  R. Ruff,et al.  Why are eye muscles frequently involved in myasthenia gravis? , 1990, Neurology.

[7]  F. Nottebohm,et al.  Neural cell adhesion molecule (N-CAM) is elevated in adult avian slow muscle fibers with multiple terminals. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[8]  L. Henderson,et al.  The single-channel basis for the slow kinetics of synaptic currents in vertebrate slow muscle fibers , 1989, Neuron.

[9]  V. E. Dionne.  Two types of nicotinic acetylcholine receptor channels at slow fibre end‐plates of the garter snake. , 1989, The Journal of physiology.

[10]  B. Sakmann,et al.  Developmental regulation of five subunit specific mRNAs encoding acetylcholine receptor subtypes in rat muscle , 1989, FEBS letters.

[11]  R. Ruff,et al.  Ocular muscles: physiology and structure-function correlations. , 1989, Bulletin de la Societe belge d'ophtalmologie.

[12]  J. Jacoby,et al.  Electrical properties and innervation of fibers in the orbital layer of rat extraocular muscles. , 1989, Journal of neurophysiology.

[13]  S. Schuetze,et al.  Embryonic acetylcholine receptors guarantee spontaneous contractions in rat developing muscle , 1988, Nature.

[14]  Z. Hall,et al.  Immunological evidence for a change in subunits of the acetylcholine receptor in developing and denervated rat muscle , 1988, Neuron.

[15]  Spencer Rf,et al.  Structural organization of the extraocular muscles. , 1988 .

[16]  J. D. Porter,et al.  Structural organization of the extraocular muscles. , 1988, Reviews of oculomotor research.

[17]  K. Oda.  Ocular Myasthenia Gravis: Antibodies to Endplates of Human Extraocular Muscle a , 1987 .

[18]  P. Brehm,et al.  Acetylcholine receptor channels on adult mouse skeletal muscle are functionally identical in synaptic and nonsynaptic membrane. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[19]  B. Sakmann,et al.  Differential regulation of muscle acetylcholine receptor gamma- and epsilon-subunit mRNAs. , 1987, FEBS letters.

[20]  K. Oda.  Motor innervation and acetylcholine receptor distribution of human extraocular muscle fibres , 1986, Journal of the Neurological Sciences.

[21]  Bert Sakmann,et al.  Molecular distinction between fetal and adult forms of muscle acetylcholine receptor , 1986, Nature.

[22]  M. Mishina,et al.  Cloning, sequencing and expression of cDNA for a novel subunit of acetylcholine receptor from calf muscle , 1985, Nature.

[23]  J. Lindstrom,et al.  Specificities of antibodies to acetylcholine receptors in sera from myasthenia gravis patients measured by monoclonal antibodies. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Davidowitz,et al.  Structure and function of extraocular muscle fibers. , 1979, Current topics in eye research.

[25]  M. Karnovsky,et al.  A "DIRECT-COLORING" THIOCHOLINE METHOD FOR CHOLINESTERASES , 1964, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.