Contribution of beta1- and beta2-adrenergic receptors to cochlear function
Main Article Content
Abstract
Sympathetic innervation is heavily present in the cochlea. However, its role in the development and maintenance of normal hearing remains debatable. Beta1-adrenergic receptors 1 (beta1-ARs) and beta2-adrenergic receptors (beta2-ARs) are two types of receptors that are stimulated by the sympathetic nervous system and are expressed by many cochlear cell types. In this study, we have analyzed the functional consequences of the lack of beta-ARs in the cochlea. We have first evaluated hearing thresholds using auditory brainstem response and distortion product otoacoustic emissions in young and aged knockout mice lacking beta1-ARs, beta2-ARs, or both beta1-ARs and beta2-ARs. Secondly, we tested the sensitivity of these mice to acoustic overexposure.
Hearing tests revealed similar normal thresholds in all beta- adrenergic receptors mice when compared to age matched wild type controls. When exposed to noise mice lacking beta1- but not beta2- AR exhibited a subtle protection of hearing thresholds at the low frequencies only. These results suggest that despite being expressed by many cochlear cell types these beta-ARs are not playing a crucial role in hearing development and maintenance.
Article Details
How to Cite
MUSTAPHA, mirna; MENDES, Diana; SMERRIGLIO, Piera.
Contribution of beta1- and beta2-adrenergic receptors to cochlear function.
Medical Research Archives, [S.l.], v. 5, n. Issue 9, sep. 2017.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1476>. Date accessed: 22 dec. 2024.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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Borg, E., 1982. Protective value of sympathectomy of the ear in noise. Acta Physiol. Scand. 115, 281–2.
Chruscinski, A.J., Rohrer, D.K., Schauble, E., Desai, K.H., Bernstein, D., Kobilka, B.K., 1999. Targeted disruption of the beta2 adrenergic receptor gene. J. Biol. Chem. 274, 16694–700.
Darrow, K.N., Simons, E.J., Dodds, L., Liberman, M.C., 2006. Dopaminergic innervation of the mouse inner ear: evidence for a separate cytochemical group of cochlear efferent fibers. J. Comp. Neurol. 498, 403–14.
Densert, O., Flock, A., 1974. An electron-microscopic study of adrenergic innervation in the cochlea. Acta Otolaryngol. 77, 185–97.
Fauser, C., Schimanski, S., Wangemann, P., 2004. Localization of beta1-adrenergic receptors in the cochlea and the vestibular labyrinth. J. Membr. Biol. 201, 25–32.
Giraudet, F., Horner, K.C., Cazals, Y., 2002. Similar half-octave TTS protection of the cochlea by xylazine/ketamine or sympathectomy. Hear. Res. 174, 239–48.
Hildesheimer, M., Henkin, Y., Pye, A., Heled, S., Sahartov, E., Shabtai, E.L., Muchnik, C., 2002. Bilateral superior cervical sympathectomy and noise-induced, permanent threshold shift in guinea pigs. Hear. Res. 163, 46–52.
Hildesheimer, M., Sharon, R., Muchnik, C., Sahartov, E., Rubinstein, M., 1991. The effect of bilateral sympathectomy on noise induced temporary threshold shift. Hear. Res. 51, 49–53.
Horner, K.C., Giraudet, F., Lucciano, M., Cazals, Y., 2001. Sympathectomy improves the ear’s resistance to acoustic trauma--could stress render the ear more sensitive? Eur. J. Neurosci. 13, 405–8.
Hozawa, K., Kimura, R.S., 1990. Cholinergic and noradrenergic nervous systems in the cynomolgus monkey cochlea. Acta Otolaryngol. 110, 46–55.
Khan, K.M., Drescher, M.J., Hatfield, J.S., Ramakrishnan, N.A., Drescher, D.G., 2007. Immunohistochemical localization of adrenergic receptors in the rat organ of corti and spiral ganglion. J. Neurosci. Res. 85, 3000–12.
LaRouere, M.J., Sillman, J.S., Nuttall, A.L., Miller, J.M., 1989. A comparison of laser Doppler and intravital microscopic measures of cochlear blood flow. Otolaryngol. Head. Neck Surg. 101, 375–84.
Laurikainen, E.A., Costa, O., Miller, J.M., Nuttall, A.L., Ren, T.Y., Masta, R., Quirk, W.S., Robinson, P.J., 1994. Neuronal regulation of cochlear blood flow in the guinea-pig. J. Physiol. 480 ( Pt 3), 563–73.
Laurikainen, E.A., Kim, D., Didier, A., Ren, T., Miller, J.M., Quirk, W.S., Nuttall, A.L., 1993. Stellate ganglion drives sympathetic regulation of cochlear blood flow. Hear. Res. 64, 199–204.
Lee, A.H., Møller, A.R., 1985. Effects of sympathetic stimulation on the round window compound action potential in the rat. Hear. Res. 19, 127–34.
Liberman, M.C., 1990. Effects of chronic cochlear de-efferentation on auditory-nerve response. Hear. Res. 49, 209–23.
Lichtensteiger, W., Spoendlin, H., 1967. Adrenergic pathways to the cochlea of the cat. Life Sci. 6, 1639–1645.
Maison, S.F., Le, M., Larsen, E., Lee, S.-K., Rosowski, J.J., Thomas, S.A., Liberman, M.C., 2010. Mice lacking adrenergic signaling have normal cochlear responses and normal resistance to acoustic injury but enhanced susceptibility to middle-ear infection. J. Assoc. Res. Otolaryngol. 11, 449–61.
Mendus, D., Sundaresan, S., Grillet, N., Wangsawihardja, F., Leu, R., Müller, U., Jones, S.M., Mustapha, M., 2014. Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear. Eur. J. Neurosci. 39, 1256–1267.
Muchnik, C., Hildesheimer, M., Nebel, L., Rubinstein, M., 1983. Influence of catecholamines on cochlear action potentials. Arch. Otolaryngol. 109, 530–2.
Ohlsén, K.A., Baldwin, D.L., Nuttall, A.L., Miller, J.M., 1991. Influence of topically applied adrenergic agents on cochlear blood flow. Circ. Res. 69, 509–18.
Pickles, J.O., 1979. An investigation of sympathetic effects on hearing. Acta Otolaryngol. 87, 69–71.
Ren, T., Laurikainen, E., Quirk, W.S., Miller, J.M., Nuttall, A.L., 1993. Effects of stellate ganglion stimulation on bilateral cochlear blood flow. Ann. Otol. Rhinol. Laryngol. 102, 378–84.
Rohrer, D.K., Chruscinski, A., Schauble, E.H., Bernstein, D., Kobilka, B.K., 1999. Cardiovascular and metabolic alterations in mice lacking both beta1- and beta2-adrenergic receptors. J. Biol. Chem. 274, 16701–8.
Rohrer, D.K., Desai, K.H., Jasper, J.R., Stevens, M.E., Regula, D.P., Barsh, G.S., Bernstein, D., Kobilka, B.K., 1996. Targeted disruption of the mouse beta1-adrenergic receptor gene: developmental and cardiovascular effects. Proc. Natl. Acad. Sci. U. S. A. 93, 7375–80.
Schimanski, S., Scofield, M.A., Wangemann, P., 2001. Functional beta2-adrenergic receptors are present in nonstrial tissues of the lateral wall in the gerbil cochlea. Audiol. Neurootol. 6, 124–31.
Sewell, W.F., 1984. The effects of furosemide on the endocochlear potential and auditory-nerve fiber tuning curves in cats. Hear. Res. 14, 305–314.
Shibamori, Y., Tamamaki, N., Saito, H., Nojyo, Y., 1994. The trajectory of the sympathetic nerve fibers to the rat cochlea as revealed by anterograde and retrograde WGA-HRP tracing. Brain Res. 646, 223–9.
Spoendlin, H., 1981. Autonomic innervation of the inner ear. Adv. Otorhinolaryngol. 27, 1–13.
Spoendlin, H., 1984. Primary Neurons and Synapses. In: Friedmann, I., Ballantyne, J. (Eds.), Ultrastructural Atlas of the Inner Ear. Butterworths, London, pp. 133-164.
Spoendlin, H., Lichtensteiger, W., 1966. The adrenergic innervation of the labyrinth. Acta Otolaryngol. 61, 423–34.
Tange, R.A., 1998. Vascular inner ear partition: a concept for some forms of sensorineural hearing loss and vertigo. ORL. J. Otorhinolaryngol. Relat. Spec. 60, 78–84.
Telischi, F.F., Mom, T., Agrama, M., Stagner, B.B., Ozdamar, O., Bustillo, A., Martin, G.K., 1999. Comparison of the auditory-evoked brainstem response wave I to distortion-product otoacoustic emissions resulting from changes to inner ear blood flow. Laryngoscope 109, 186–91.
Telischi, F.F., Stagner, B., Widick, M.P., Balkany, T.J., Lonsbury-Martin, B.L., 1998. Distortion-product otoacoustic emission monitoring of cochlear blood flow. Laryngoscope 108, 837–42.
Wang, X., Robertson, D., 1997. Two types of actions of norepinephrine on identified auditory efferent neurons in rat brain stem slices. J. Neurophysiol. 78, 1800–10.
Wangemann, P., 2002. Adrenergic and muscarinic control of cochlear endolymph production. Adv. Otorhinolaryngol. 59, 42–50.
Wangemann, P., Liu, J., Marcus, D.C., 1995. Ion transport mechanisms responsible for K+ secretion and the transepithelial voltage across marginal cells of stria vascularis in vitro. Hear. Res. 84, 19–29.
Wangemann, P., Liu, J., Scherer, E.Q., Herzog, M., Shimozono, M., Scofield, M.A., 2001. Muscarinic receptors control K+ secretion in inner ear strial marginal cells. J. Membr. Biol. 182, 171–81.
Wangemann, P., Liu, J., Shimozono, M., Schimanski, S., Scofield, M.A., 2000. K+ secretion in strial marginal cells is stimulated via beta 1-adrenergic receptors but not via beta 2-adrenergic or vasopressin receptors. J. Membr. Biol. 175, 191–202.
Wangemann, P., Wonneberger, K., 2005. Neurogenic regulation of cochlear blood flow occurs along the basilar artery, the anterior inferior cerebellar artery and at branch points of the spiral modiolar artery. Hear. Res. 209, 91–6.
Warr,W.B., 1992. Organization of Olivocochlear Efferent System in Mammals. In: Webster, D.B., Popper, A.N., Fay, R.R. (Eds.), Mammalian Auditory Pathway: Neuroanatomy. Springer, New York, pp. 410-448.
Warr, W.B., Guinan J.J., White J.S., 1986. Organization of efferent fibers: The lateral and medial olivocochlear systems. In: Altschuler, R.A., Hoffman, D.W., Bobbin, R.P. (Eds.), Neurobiology of Hearing: The Cochlea, Raven, New York, pp. 333–348.
Borg, E., 1982. Protective value of sympathectomy of the ear in noise. Acta Physiol. Scand. 115, 281–2.
Chruscinski, A.J., Rohrer, D.K., Schauble, E., Desai, K.H., Bernstein, D., Kobilka, B.K., 1999. Targeted disruption of the beta2 adrenergic receptor gene. J. Biol. Chem. 274, 16694–700.
Darrow, K.N., Simons, E.J., Dodds, L., Liberman, M.C., 2006. Dopaminergic innervation of the mouse inner ear: evidence for a separate cytochemical group of cochlear efferent fibers. J. Comp. Neurol. 498, 403–14.
Densert, O., Flock, A., 1974. An electron-microscopic study of adrenergic innervation in the cochlea. Acta Otolaryngol. 77, 185–97.
Fauser, C., Schimanski, S., Wangemann, P., 2004. Localization of beta1-adrenergic receptors in the cochlea and the vestibular labyrinth. J. Membr. Biol. 201, 25–32.
Giraudet, F., Horner, K.C., Cazals, Y., 2002. Similar half-octave TTS protection of the cochlea by xylazine/ketamine or sympathectomy. Hear. Res. 174, 239–48.
Hildesheimer, M., Henkin, Y., Pye, A., Heled, S., Sahartov, E., Shabtai, E.L., Muchnik, C., 2002. Bilateral superior cervical sympathectomy and noise-induced, permanent threshold shift in guinea pigs. Hear. Res. 163, 46–52.
Hildesheimer, M., Sharon, R., Muchnik, C., Sahartov, E., Rubinstein, M., 1991. The effect of bilateral sympathectomy on noise induced temporary threshold shift. Hear. Res. 51, 49–53.
Horner, K.C., Giraudet, F., Lucciano, M., Cazals, Y., 2001. Sympathectomy improves the ear’s resistance to acoustic trauma--could stress render the ear more sensitive? Eur. J. Neurosci. 13, 405–8.
Hozawa, K., Kimura, R.S., 1990. Cholinergic and noradrenergic nervous systems in the cynomolgus monkey cochlea. Acta Otolaryngol. 110, 46–55.
Khan, K.M., Drescher, M.J., Hatfield, J.S., Ramakrishnan, N.A., Drescher, D.G., 2007. Immunohistochemical localization of adrenergic receptors in the rat organ of corti and spiral ganglion. J. Neurosci. Res. 85, 3000–12.
LaRouere, M.J., Sillman, J.S., Nuttall, A.L., Miller, J.M., 1989. A comparison of laser Doppler and intravital microscopic measures of cochlear blood flow. Otolaryngol. Head. Neck Surg. 101, 375–84.
Laurikainen, E.A., Costa, O., Miller, J.M., Nuttall, A.L., Ren, T.Y., Masta, R., Quirk, W.S., Robinson, P.J., 1994. Neuronal regulation of cochlear blood flow in the guinea-pig. J. Physiol. 480 ( Pt 3), 563–73.
Laurikainen, E.A., Kim, D., Didier, A., Ren, T., Miller, J.M., Quirk, W.S., Nuttall, A.L., 1993. Stellate ganglion drives sympathetic regulation of cochlear blood flow. Hear. Res. 64, 199–204.
Lee, A.H., Møller, A.R., 1985. Effects of sympathetic stimulation on the round window compound action potential in the rat. Hear. Res. 19, 127–34.
Liberman, M.C., 1990. Effects of chronic cochlear de-efferentation on auditory-nerve response. Hear. Res. 49, 209–23.
Lichtensteiger, W., Spoendlin, H., 1967. Adrenergic pathways to the cochlea of the cat. Life Sci. 6, 1639–1645.
Maison, S.F., Le, M., Larsen, E., Lee, S.-K., Rosowski, J.J., Thomas, S.A., Liberman, M.C., 2010. Mice lacking adrenergic signaling have normal cochlear responses and normal resistance to acoustic injury but enhanced susceptibility to middle-ear infection. J. Assoc. Res. Otolaryngol. 11, 449–61.
Mendus, D., Sundaresan, S., Grillet, N., Wangsawihardja, F., Leu, R., Müller, U., Jones, S.M., Mustapha, M., 2014. Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear. Eur. J. Neurosci. 39, 1256–1267.
Muchnik, C., Hildesheimer, M., Nebel, L., Rubinstein, M., 1983. Influence of catecholamines on cochlear action potentials. Arch. Otolaryngol. 109, 530–2.
Ohlsén, K.A., Baldwin, D.L., Nuttall, A.L., Miller, J.M., 1991. Influence of topically applied adrenergic agents on cochlear blood flow. Circ. Res. 69, 509–18.
Pickles, J.O., 1979. An investigation of sympathetic effects on hearing. Acta Otolaryngol. 87, 69–71.
Ren, T., Laurikainen, E., Quirk, W.S., Miller, J.M., Nuttall, A.L., 1993. Effects of stellate ganglion stimulation on bilateral cochlear blood flow. Ann. Otol. Rhinol. Laryngol. 102, 378–84.
Rohrer, D.K., Chruscinski, A., Schauble, E.H., Bernstein, D., Kobilka, B.K., 1999. Cardiovascular and metabolic alterations in mice lacking both beta1- and beta2-adrenergic receptors. J. Biol. Chem. 274, 16701–8.
Rohrer, D.K., Desai, K.H., Jasper, J.R., Stevens, M.E., Regula, D.P., Barsh, G.S., Bernstein, D., Kobilka, B.K., 1996. Targeted disruption of the mouse beta1-adrenergic receptor gene: developmental and cardiovascular effects. Proc. Natl. Acad. Sci. U. S. A. 93, 7375–80.
Schimanski, S., Scofield, M.A., Wangemann, P., 2001. Functional beta2-adrenergic receptors are present in nonstrial tissues of the lateral wall in the gerbil cochlea. Audiol. Neurootol. 6, 124–31.
Sewell, W.F., 1984. The effects of furosemide on the endocochlear potential and auditory-nerve fiber tuning curves in cats. Hear. Res. 14, 305–314.
Shibamori, Y., Tamamaki, N., Saito, H., Nojyo, Y., 1994. The trajectory of the sympathetic nerve fibers to the rat cochlea as revealed by anterograde and retrograde WGA-HRP tracing. Brain Res. 646, 223–9.
Spoendlin, H., 1981. Autonomic innervation of the inner ear. Adv. Otorhinolaryngol. 27, 1–13.
Spoendlin, H., 1984. Primary Neurons and Synapses. In: Friedmann, I., Ballantyne, J. (Eds.), Ultrastructural Atlas of the Inner Ear. Butterworths, London, pp. 133-164.
Spoendlin, H., Lichtensteiger, W., 1966. The adrenergic innervation of the labyrinth. Acta Otolaryngol. 61, 423–34.
Tange, R.A., 1998. Vascular inner ear partition: a concept for some forms of sensorineural hearing loss and vertigo. ORL. J. Otorhinolaryngol. Relat. Spec. 60, 78–84.
Telischi, F.F., Mom, T., Agrama, M., Stagner, B.B., Ozdamar, O., Bustillo, A., Martin, G.K., 1999. Comparison of the auditory-evoked brainstem response wave I to distortion-product otoacoustic emissions resulting from changes to inner ear blood flow. Laryngoscope 109, 186–91.
Telischi, F.F., Stagner, B., Widick, M.P., Balkany, T.J., Lonsbury-Martin, B.L., 1998. Distortion-product otoacoustic emission monitoring of cochlear blood flow. Laryngoscope 108, 837–42.
Wang, X., Robertson, D., 1997. Two types of actions of norepinephrine on identified auditory efferent neurons in rat brain stem slices. J. Neurophysiol. 78, 1800–10.
Wangemann, P., 2002. Adrenergic and muscarinic control of cochlear endolymph production. Adv. Otorhinolaryngol. 59, 42–50.
Wangemann, P., Liu, J., Marcus, D.C., 1995. Ion transport mechanisms responsible for K+ secretion and the transepithelial voltage across marginal cells of stria vascularis in vitro. Hear. Res. 84, 19–29.
Wangemann, P., Liu, J., Scherer, E.Q., Herzog, M., Shimozono, M., Scofield, M.A., 2001. Muscarinic receptors control K+ secretion in inner ear strial marginal cells. J. Membr. Biol. 182, 171–81.
Wangemann, P., Liu, J., Shimozono, M., Schimanski, S., Scofield, M.A., 2000. K+ secretion in strial marginal cells is stimulated via beta 1-adrenergic receptors but not via beta 2-adrenergic or vasopressin receptors. J. Membr. Biol. 175, 191–202.
Wangemann, P., Wonneberger, K., 2005. Neurogenic regulation of cochlear blood flow occurs along the basilar artery, the anterior inferior cerebellar artery and at branch points of the spiral modiolar artery. Hear. Res. 209, 91–6.
Warr,W.B., 1992. Organization of Olivocochlear Efferent System in Mammals. In: Webster, D.B., Popper, A.N., Fay, R.R. (Eds.), Mammalian Auditory Pathway: Neuroanatomy. Springer, New York, pp. 410-448.
Warr, W.B., Guinan J.J., White J.S., 1986. Organization of efferent fibers: The lateral and medial olivocochlear systems. In: Altschuler, R.A., Hoffman, D.W., Bobbin, R.P. (Eds.), Neurobiology of Hearing: The Cochlea, Raven, New York, pp. 333–348.