Artículo

La versión final de este artículo es de uso interno. El editor solo permite incluir en el repositorio el artículo en su versión post-print. Por favor, si usted la posee enviela a
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Spinal nucleus of bulbocavernosus and its target musculature, the bulbocavernosus and levator ani muscles, are sexually dimorphic, and their sexual differentiation depends on plasmatic levels of testosterone. Electrophysiological and immunocytochemical studies have demonstrated that at mammalian adult neuromuscular junctions only P/Q-type Ca2+ channels (Cav2.1), mediate evoked transmitter release. Here we report that N-type Ca2+ channel (Cav2.2) blocker ω-Conotoxin GVIA, as well as Cav2.1 blocker ω-Agatoxin IVA, significantly reduced quantal content of transmitter release by ∼ 80% and ∼70% respectively at levator ani muscle of the adult rats, indicating that neuromuscular transmission is jointly mediated by both types of channels. In these synapses, we also observed that castration and restitution of plasmatic testosterone in rats resulted in changes in the sensitivity to ω-Conotoxin GVIA. Castration induced, whereas testosterone treatment avoided, functional loss of Cav2.2, as mediators of transmitter release in these synapses. Strikingly, the expression and localization of α1B subunits, which form the pore of the Cav2.2 channel, were similar at control, gonadectomized and gonadectomized testosterone-treated rats, suggesting that testosterone may regulate the coupling mechanisms between Ca v2.2 and transmitter release at the neuromuscular junctions of these sexually dimorphic motoneurons. © 2005 IBRO. Published by Elsevier Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:Testosterone modulates Cav2.2 calcium channels' functional expression at rat levator ani neuromuscular junction
Autor:Nudler, S.I.; Pagani, M.R.; Urbano, F.J.; McEnery, M.W.; Uchitel, O.D.
Filiación:Departamento de Fisiología, Biología Molecular Y Celular, Facultad de Ciencias Exactas Y Naturales, Pabellón II-2do Piso, Buenos Aires, 1428, Argentina
Department of General Medical Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, United States
Instituto de Neurociencias, Universidad Miguel Hernández, CSIC Campus de San Juan, 03550 San Juan de Alicante, Spain
Palabras clave:ω-Conotoxin GVIA; Bulbocavernosus; Gonadectomy; Immunostaining; Synaptic transmission; Testosterone propionate; calcium channel; calcium channel blocking agent; calcium channel N type; conotoxin; protein subunit; testosterone; animal tissue; article; castration; controlled study; gonadectomy; hormone action; levator ani muscle; male; motoneuron; neuromuscular synapse; neuromuscular transmission; neurotransmitter release; nonhuman; priority journal; protein expression; protein function; protein localization; rat; sensitivity analysis; synapse; Animals; Animals, Newborn; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, N-Type; Diaphragm; Drug Interactions; Evoked Potentials; Gene Expression Regulation; Immunohistochemistry; Male; Neuromuscular Junction; omega-Agatoxin IVA; omega-Conotoxin GVIA; Orchiectomy; Pelvic Floor; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Cholinergic; Testosterone
Año:2005
Volumen:134
Número:3
Página de inicio:817
Página de fin:826
DOI: http://dx.doi.org/10.1016/j.neuroscience.2005.03.061
Título revista:Neuroscience
Título revista abreviado:Neuroscience
ISSN:03064522
CODEN:NRSCD
CAS:testosterone, 58-22-0; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, N-Type; Cav2.2 protein, rat; omega-Agatoxin IVA; omega-Conotoxin GVIA, 92078-76-7; Receptors, Cholinergic; Testosterone, 58-22-0
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064522_v134_n3_p817_Nudler

Referencias:

  • Arnold, A.P., Gorski, R.A., Gonadal steroid induction of structural sex differences in the central nervous system (1984) Annu Rev Neurosci, 7, pp. 413-442
  • Arnold, A.P., Bbottjer, S.W., Nordeen, E.J., Nordeen, K.W., Sengelaub, D.R., Hormones and critical periods in behavioral and neural development (1987) Imprinting and Cortical Plasticity, pp. 55-97. , J.P. Rauschecker P. Marier John Wiley New York
  • Beato, M., Truss, M., Chavez, S., Control of transcription by steroid hormones (1996) Ann N Y Acad Sci, 784, pp. 93-123
  • Bowersox, S.S., Miljanich, G.P., Sugiura, Y., Li, C., Nadasdi, L., Hoffman, B.B., Ramachandran, J., Ko, C.P., Differential blockade of voltage-sensitive calcium channels at the mouse neuromuscular junction by novel omega-conopeptides and omega-agatoxin-IVA (1995) J Pharmacol Exp Ther, 273 (1), pp. 248-256
  • Breedlove, S.M., Arnold, A.P., Hormone accumulation in a sexually dimorphic motor nucleus of the rat spinal cord (1980) Science, 210 (4469), pp. 564-566
  • Breedlove, S.M., Arnold, A.P., Sexually dimorphic motor nucleus in the rat lumbar spinal cord: Response to adult hormone manipulation, absence in androgen-insensitive rats (1981) Brain Res, 225 (2), pp. 297-307
  • Breedlove, S.M., Arnold, A.P., Hormonal control of a developing neuromuscular system. I. Complete demasculinization of the male rat spinal nucleus of the bulbocavernosus using the anti-androgenflutamide (1983) J Neurosci, 3 (2), pp. 417-423
  • Breedlove, S.M., Arnold, A.P., Hormonal control of a developing neuromuscular system. II. Sensitive periods for the androgen-induced masculinization of the rat spinal nucleus of the bulbocavernosus (1983) J Neurosci, 3 (2), pp. 424-432
  • Breedlove, S.M., Sexual dimorphism in the vertebrate nervous system (1992) J Neurosci, 12 (11), pp. 4133-4142
  • Burke, K.A., Widows, M.R., Sengelaub, D.R., Synergistic effects of testosterone metabolites on the development of motoneuron morphology in a sexually dimorphic rat spinal nucleus (1997) J Neurobiol, 33 (1), pp. 1-10
  • Callies, F., Kollenkirchen, U., Von Zur Muhlen, C., Tomaszewski, M., Beer, S., Allolio, B., Testosterone undecanoate: A useful tool for testosterone administration in rats (2003) Exp Clin Endocrinol Diabetes, 111 (4), pp. 203-208
  • Catterall, W.A., Structure and regulation of voltage-gated Ca2+ channels (2000) Annu Rev Cell Dev Biol, 16, pp. 521-555
  • Cihak, R., Gutmann, E., Hanzlikova, V., Involution and hormone-induced persistence of the M. sphincter (levator) ani in female rats (1970) J Anat., 106 (1), pp. 93-110
  • Cohen-Cory, S., The developing synapse: Construction and modulation of synaptic structures and circuits (2002) Science, 298, pp. 770-776
  • Day, N.C., Wood, S.J., Ince, P.G., Volsen, S.G., Smith, W., Slater, C.R., Shaw, P.J., Differential localization of voltage-dependent calcium channel alpha1 subunits at the human and rat neuromuscular junction (1997) J Neurosci, 17 (16), pp. 6226-6235
  • Dube, J.Y., Lesage, R., Tremblay, R.R., Androgen and estrogen binding in rat skeletal and perineal muscles (1976) Can J Biochem., 54 (1), pp. 50-55
  • Fields, R.D., Yu, C., Nelson, P.G., Calcium, network activity, and the role of NMDA channels in synaptic plasticity in vitro (1991) J Neurosci, 11, pp. 134-146
  • Forger, N.G., Breedlove, S.M., Seasonal variation in mammalian striated muscle mass and motoneuron morphology (1987) J Neurobiol, 18 (2), pp. 155-165
  • García-Segura, L.M., Chowen, J.A., Párducz, A., Naftolin, N., Gonadal hormones as promoters of structural synaptic plasticity: Cellular mechanisms (1994) Prog Neurobiol, 44, pp. 279-307
  • Goldstein, L.A., Kurz, E.M., Sengelaub, D.R., Androgen regulation of dendritic growth and retraction in the development of a sexually dimorphic spinal nucleus (1990) J Neurosci, 10 (3), pp. 935-946
  • Goldstein, L.A., Sengelaub, D.R., Hormonal control of neuron number in sexually dimorphic spinal nuclei of the rat: IV. Masculinization of the spinal nucleus of the bulbocavernosus with testosterone metabolites (1990) J Neurobiol, 21 (5), pp. 719-730
  • Hubbard, J.I., Llinás, R., Quastel, D.M.J., (1969) Electrophysiological Analysis of Synaptic Transmission, , Edward Arnold (Publishers) Ltd London
  • Iwasaki, S., Takahashi, T., Developmental changes in calcium channel types mediating synaptic transmission in rat auditory brainstem (1998) J Physiol, 509 (PART 2), pp. 419-423
  • Iwasaki, S., Momiyama, A., Uchitel, O.D., Takahashi, T., Developmental changes in calcium channel types mediating central synaptic transmission (2000) J Neurosci 2000, 20 (1), pp. 59-65
  • Jordan, C.L., Letinsky, M.S., Arnold, A.P., Synapse elimination occurs late in the hormone-sensitive levator ani muscle of the rat (1988) J Neurobiol, 19 (4), pp. 335-356
  • Jordan, C.L., Pawson, P.A., Arnold, A.P., Grinnell, A.D., Hormonal regulation of motor unit size and synaptic strength during synapse elimination in the rat levator ani muscle (1992) J Neurosci, 12 (11), pp. 4447-4459
  • Jost, A., Genetic and hormonal factors in sex differentiation of the brain (1983) Psychoneuroendocrinology 1983, 8 (2), pp. 183-193
  • Katz, B., (1969) The Release of Neural Transmitter Substances, , Liverpool University Press Liverpool
  • Katz, E., Protti, D.A., Ferro, P.A., Rosato Siri, M.D., Uchitel, O.D., Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction (1997) Br J Pharmacol, 121 (8), pp. 1531-1540
  • Kawata, M., Roles of steroid hormones and their receptors in structural organization in the nervous system (1995) Neurosci Res, 24 (1), pp. 1-46
  • Keast, J.R., Effects of testosterone on pelvic autonomic pathways: Progress and pitfalls (2000) J Auton Nerv Syst, 79 (2-3), pp. 67-73
  • Krieg, M., Dennis, M., Voigt, K.D., Comparison between the binding of 19-nortestosterone, 5alpha-dihydrotestosterone and testosterone in rat prostate and bulbocavernosus/levator ani muscle (1976) J Endocrinol, 70 (3), pp. 379-387
  • Matsumoto, A., Arnold, A.P., Zampighi, G.A., Micevych, P.E., Androgenic regulation of gap junctions between motoneurons in the rat spinal cord (1988) J Neurosci, 8 (11), pp. 4177-4183
  • Matsumoto, A., Arai, Y., Prins, G.S., Androgenic regulation of androgen receptor immunoreactivity in motoneurons of the spinal nucleus of the bulbocavernosus of male rats (1996) J Neuroendocrinol, 8 (7), pp. 553-559
  • Normann, C., Peckys, D., Schulze, C.H., Walden, J., Jonas, P., Bischofberger, J., Associative long-term depression in the hippocampus is dependent on postsynaptic N-type Ca2+ channels (2000) J Neurosci, 20 (22), pp. 8290-8297
  • Pagani, R., Song, M., McEnery, M., Qin, N., Tsien, R.W., Toro, L., Stefani, E., Uchitel, O.D., Differential expression of alpha 1 and beta subunits of voltage dependent Ca2+ channel at the neuromuscular junction of normal and P/Q Ca2+ channel knockout mouse (2004) Neuroscience, 123 (1), pp. 75-85
  • Protti, D.A., Szczupak, L., Scornik, F.S., Uchitel, O.D., Effect of omega-conotoxin GVIA on neurotransmitter release at the mouse neuromuscular junction (1991) Brain Res, 557 (1-2), pp. 336-339
  • Protti, D.A., Uchitel, O.D., Transmitter release and presynaptic Ca2+ currents blocked by the spider toxin omega-Aga-IVA (1993) Neuroreport, 5 (3), pp. 333-336
  • Racchi, M., Govoni, S., Solerte, S.B., Galli, C.L., Corsini, E., Dehydroepiandrosterone and the relationship with aging and memory: A possible link with protein kinase C functional machinery (2001) Brain Res Rev, 37, pp. 287-293
  • Rand, M.N., Breedlove, S.M., Androgen locally regulates rat bulbocavernosus and levator ani size (1992) J Neurobiol, 23 (1), pp. 17-30
  • Reilly, C.M., Stopper, V.S., Mills, T.M., Androgens modulate the alpha-adrenergic responsiveness of vascular smooth muscle in the corpus cavernosum (1997) J Androl, 18, pp. 26-31
  • Resko, J.A., Norman, R.L., Niswender, G.D., Spies, H.G., The relationship between progestins and gonadotropins during the late luteal phase of the menstrual cycle in rhesus monkeys (1974) Endocrinology, 94 (1), pp. 128-135
  • Rosato Siri, M.D., Uchitel, O.D., Calcium channels coupled to neurotransmitter release at neonatal rat neuromuscular junctions (1999) J Physiol, 514 (PART 2), pp. 533-540
  • Rupprecht, R., Holsboer, F., Neuroactive steroids: Mechanisms of action and neuropsychopharmacological perspectives (1999) Trends Neurosci, 22 (9), pp. 410-416
  • Sachs, B.D., Role of striated penile muscles in penile reflexes, copulation, and induction of pregnancy in the rat (1982) J Reprod Fertil, 66 (2), pp. 433-443
  • Schirar, A., Chang, C., Rousseau, J.P., Localization of androgen receptor in nitric oxide synthase- and vasoactive intestinal peptide-containing neurons of the major pelvic ganglion innervating the rat penis (1997) J Neuroendocrinol, 9 (2), pp. 141-150
  • Sengelaub, D.R., Jordan, C.L., Kurz, E.M., Arnold, A.P., Hormonal control of neuron number in sexually dimorphic spinal nuclei of the rat: II. Development of the spinal nucleus of the bulbocavernosus in androgen-insensitive (Tfm) rats (1989) J Comp Neurol, 280 (4), pp. 630-636
  • Souccar, C., Lapa, A.J., Do Valle, J.R., The influence of testosterone on neuromuscular transmission in hormone sensitive mammalian skeletal muscles (1982) Muscle Nerve, 5 (3), pp. 232-237
  • Steiner, A.L., Pagliara, A.S., Chase, L.R., Kipnis, D.M., Radioimmunoassay for cyclic nucleotides. II. Adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in mammalian tissues and body fluids (1972) J Biol Chem, 247 (4), pp. 1114-1120
  • Taylor, S.R., Widows, M.R., Sengelaub, D.R., Estrogenic influence and possible site of action in development of motoneuron morphology in a sexually dimorphic rat spinal nucleus (1995) Soc Neurosci Abstr, 21, p. 40
  • Uchitel, O.D., Protti, D.A., Sanchez, V., Cherksey, B.D., Sugimori, M., Llinas, R., P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses (1992) Proc Natl Acad Sci U S a, 89 (8), pp. 3330-3333
  • Vance, C.L., Begg, C.M., Lee, W.L., Haase, H., Copeland, T.D., McEnery, M.W., Differential expression and association of calcium channel alpha1B and beta subunits during rat brain ontogeny (1998) J Biol Chem, 273, pp. 14495-14502
  • Wu, S.N., Jan, C.R., Li, H.F., Characteristics of store-operated Ca2+-permeable current in monocytic U937 cells (1997) Chin J Physiol, 40 (3), pp. 115-120
  • Yamamoto, L.A., Lapa, A.J., Souccar, C., Prejunctional regulatory actions of androgens on a hormone sensitive muscle (1994) Muscle Nerve, 17 (8), pp. 906-912

Citas:

---------- APA ----------
Nudler, S.I., Pagani, M.R., Urbano, F.J., McEnery, M.W. & Uchitel, O.D. (2005) . Testosterone modulates Cav2.2 calcium channels' functional expression at rat levator ani neuromuscular junction. Neuroscience, 134(3), 817-826.
http://dx.doi.org/10.1016/j.neuroscience.2005.03.061
---------- CHICAGO ----------
Nudler, S.I., Pagani, M.R., Urbano, F.J., McEnery, M.W., Uchitel, O.D. "Testosterone modulates Cav2.2 calcium channels' functional expression at rat levator ani neuromuscular junction" . Neuroscience 134, no. 3 (2005) : 817-826.
http://dx.doi.org/10.1016/j.neuroscience.2005.03.061
---------- MLA ----------
Nudler, S.I., Pagani, M.R., Urbano, F.J., McEnery, M.W., Uchitel, O.D. "Testosterone modulates Cav2.2 calcium channels' functional expression at rat levator ani neuromuscular junction" . Neuroscience, vol. 134, no. 3, 2005, pp. 817-826.
http://dx.doi.org/10.1016/j.neuroscience.2005.03.061
---------- VANCOUVER ----------
Nudler, S.I., Pagani, M.R., Urbano, F.J., McEnery, M.W., Uchitel, O.D. Testosterone modulates Cav2.2 calcium channels' functional expression at rat levator ani neuromuscular junction. Neuroscience. 2005;134(3):817-826.
http://dx.doi.org/10.1016/j.neuroscience.2005.03.061