Volume 16 Supplement 1

Abstracts from the 7th International Conference on cGMP Generators, Effectors and Therapeutic Implications

Open Access

Differential role of NO-sensitive guanylyl cyclase isoforms NO-GC1 and NO-GC2 in auditory function in adult mice

  • Dorit Möhrle1Email author,
  • Nicole Eichert1,
  • Steffen Wolter1,
  • Evanthia Mergia2,
  • Doris Koesling2,
  • Andreas Friebe3,
  • Marlies Knipper1 and
  • Lukas Rüttiger1
BMC Pharmacology and Toxicology201516(Suppl 1):A69

https://doi.org/10.1186/2050-6511-16-S1-A69

Published: 2 September 2015

Background

In the inner ear, elevated cyclic guanosine 3’-5’-monophospate (cGMP) levels were shown to have a sheltering role for cochlear hair cells and hearing function [1]. However, the individual roles of the two nitric oxide-sensitive guanylyl cyclase isoforms (NO-GC1 and NO-GC2) as cGMP generators in this protective effect are still unclear.

The aim of this study was to investigate how the deletion of either one of the α-subunits of NO-GC (NO-GC1 KO or NO-GC2 KO) [2] or deletion of the β1-subunit of NO-GC (NO-GC KO), leading to global lack of NO-GC expression [3], affects hearing function, vulnerability to noise exposure and recovery from acoustic trauma in mice.

Materials and methods

Hearing thresholds and supra-threshold auditory processing at sensation level of NO-GC knockout and wildtype mice were analyzed by measuring the auditory brainstem responses (ABRs). Outer hair cell function was assessed by the distortion product of the otoacoustic emissions (DPOAEs). ABRs and DPOAEs were recorded before and after exposure to intense noise (8-16 kHz, 120 dB SPL, 1 h). Immunohistochemistry was performed on cochlear sections.

Results

NO-GC1 KO, NO-GC2 KO, and NO-GC KO mice strains showed similar hearing thresholds, outer hair cell function, and amplitudes of ABRs on the level of the auditory nerve fibers, but showed differences in vulnerability to acoustic noise exposure.

Conclusion

Comparison of the NO-GC knockout with the wildtype mice suggests non-redundant roles of the two NO-GC isoforms in auditory function. The results will be discussed regarding NO-GC as a proposed cGMP generator in functionally distinct parts of the auditory pathway and considering NO/cGMP-signaling as an otoprotective cascade after noise-induced damage of the ear.

Declarations

Acknowledgement

This work was supported by grants from the Deutsche Forschungsgemeinschaft (FOR 2060 project FE 438/5-1).

Authors’ Affiliations

(1)
Department of Otolaryngology, Eberhard-Karls-Universität
(2)
Department of Pharmacology and Toxicology, Ruhr-Universität
(3)
Department of Physiology, Julius-Maximilians-Universität

References

  1. Jaumann M, Dettling J, Gubelt M, Zimmermann U, Gerling A, Paquet-Durand F, et al: cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function. Nat Med. 2012, 18 (2): 252-259. 10.1038/nm.2634.View ArticlePubMedGoogle Scholar
  2. Mergia E, Friebe A, Dangel O, Russwurm M, Koesling D: Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular system. J Clin Invest. 2006, 116 (6): 1731-1737. 10.1172/JCI27657.View ArticlePubMedPubMed CentralGoogle Scholar
  3. Friebe A, Mergia E, Dangel O, Lange A, Koesling D: Fatal gastrointestinal obstruction and hypertension in mice lacking nitric oxide-sensitive guanylyl cyclase. Proc Natl Acad Sci. 2007, 104 (18): 7699-7704. 10.1073/pnas.0609778104.View ArticlePubMedPubMed CentralGoogle Scholar

Copyright

© Möhrle et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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