Abstract
ERG (ether-a-go-go-related gene) channels are the members of the voltage-dependent potassium channel family, which have three subtypes, as ERG1 (Kv 11.1), ERG2 (Kv 11.2), and ERG3 (Kv11.3). There is no information on ERG channels in the cochlear nucleus (CN) neurons, which is the first relay station of the auditory pathway. As occur in some of congenital long QT Syndromes (LQTS), mutation of the KCNQ11 genes for ERG channel has been reported to be accompanied by hearing loss. For that reason, we aimed to study biophysical properties and physiological importance, and contribution of ERG K+ currents to the formation of action potentials in the stellate and bushy neurons of the ventral cochlear nucleus (VCN). A total of 70 mice at 14–17 days old were used for this study. Electrophysiological characterization of ERG channels was performed using patch-clamp technique in the CN slices. In current clamp, ERG channel blockers, terfenadine (10 µM) and E-4031 (10 µM), were applied in both cell types. The activation, inactivation, and deactivation kinetics of the ERG channels were determined by voltage clamp. In conclusion, the findings obtained in the present study suggest that stellate and bushy neurons express ERG channels and ERG channels appear to contribute to setting action potential (AP) frequency, threshold for AP induction, and, possibly, resting membrane potentials in this cells.
Similar content being viewed by others
References
Bal R, Baydas G (2009) Electrophysiological properties of octopus neurons of the cat cochlear nucleus: an in vitro study. J Assoc Res Otolaryngol 10:281–293. https://doi.org/10.1007/s10162-009-0159-x
Bal R, Baydas G, Naziroglu M (2009) Electrophysiological properties of ventral cochlear nucleus neurons of the dog. Hear Res 256:93–103. https://doi.org/10.1016/j.heares.2009.07.004
Bal R, Oertel D (2000) Hyperpolarization-activated, mixed-cation current (I(h)) in octopus cells of the mammalian cochlear nucleus. J Neurophysiol 84:806–817
Bal R, Oertel D (2001a) Potassium currents in octopus cells of the mammalian cochlear nucleus. J Neurophysiol 86:2299–2311
Bal R, Oertel D (2001b) Potassium currents in octopus cells of the mammalian cochlear nucleus. J Neurophysiol 86:2299–2311
Bal R, Oertel D (2007) Voltage-activated calcium currents in octopus cells of the mouse cochlear nucleus. J Assoc Res Otolaryngol 8:509–521. https://doi.org/10.1007/s10162-007-0091-x
Bal R et al (2018) Modulation of excitability of stellate neurons in the ventral cochlear nucleus of mice by ATP-sensitive potassium channels. J Membr Biol 251:163–178. https://doi.org/10.1007/s00232-017-0011-x
Bauer CK, Schafer R, Schiemann D, Reid G, Hanganu I, Schwarz JR (1999) A functional role of the erg-like inward-rectifying K+ current in prolactin secretion from rat lactotrophs. Mol Cell Endocrinol 148:37–45. https://doi.org/10.1016/S0303-7207(98)00241-X
Chen L, Sampson KJ, Kass RS (2016) Cardiac delayed rectifier potassium channels in health and disease. Cardiac Electrophysiol Clin 8:307–322. https://doi.org/10.1016/j.ccep.2016.01.004
Ferragamo MJ, Golding NL, Oertel D (1998) Synaptic inputs to stellate cells in the ventral cochlear nucleus. J Neurophysiol 79:51–63
Ferragamo MJ, Oertel D (2002) Octopus cells of the mammalian ventral cochlear nucleus sense the rate of depolarization. J Neurophysiol 87:2262–2270. https://doi.org/10.1152/jn.00587.2001
Forscher P, Oxford GS (1985) Modulation of calcium channels by norepinephrine in internally dialyzed avian sensory neurons. J Gen Physiol 85:743–763
Guasti L et al (2005) Expression pattern of the ether-a-go-go-related (ERG) family proteins in the adult mouse central nervous system: evidence for coassembly of different subunits. J Comp Neurol 491:157–174. https://doi.org/10.1002/cne.20721
Hardman RM, Forsythe ID (2009) Ether-a-go-go-related gene K+ channels contribute to threshold excitability of mouse auditory brainstem neurons. J Physiol 587:2487–2497. https://doi.org/10.1113/jphysiol.2009.170548
Hirdes W, Schweizer M, Schuricht KS, Guddat SS, Wulfsen I, Bauer CK, Schwarz JR (2005) Fast erg K+ currents in rat embryonic serotonergic neurones. J Physiol 564:33–49. https://doi.org/10.1113/jphysiol.2004.082123
Jin Z, Uhlen I, Wei-Jia K, Mao-Li D (2009) Cochlear homeostasis and its role in genetic deafness. J Otol 4:15–22
Manis PB, Marx SO (1991) Outward currents in isolated ventral cochlear nucleus neurons. J Neurosci 11:2865–2880
Niculescu D, Hirdes W, Hornig S, Pongs O, Schwarz JR (2013) Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation. J Neurosci 33:16729–16740. https://doi.org/10.1523/JNEUROSCI.5523-12.2013
Oertel D, Bal R, Gardner SM, Smith PH, Joris PX (2000) Detection of synchrony in the activity of auditory nerve fibers by octopus cells of the mammalian cochlear nucleus. Proc Natl Acad Sci USA 97:11773–11779. https://doi.org/10.1073/pnas.97.22.11773
Oertel D, Wright S, Cao XJ, Ferragamo M, Bal R (2011) The multiple functions of T stellate/multipolar/chopper cells in the ventral cochlear nucleus. Hear Res 276:61–69. https://doi.org/10.1016/j.heares.2010.10.018
Oertel D, Wu SH, Garb MW, Dizack C (1990) Morphology and physiology of cells in slice preparations of the posteroventral cochlear nucleus of mice. J Comp Neurol 295:136–154. https://doi.org/10.1002/cne.902950112
Pessia M et al (2008) ERG voltage-gated K+ channels regulate excitability and discharge dynamics of the medial vestibular nucleus neurones. J Physiol 586:4877–4890. https://doi.org/10.1113/jphysiol.2008.155762
Piper DR, Hinz WA, Tallurri CK, Sanguinetti MC, Tristani-Firouzi M (2005) Regional specificity of human ether-a’-go-go-related gene channel activation and inactivation gating. J Biol Chem 280:7206–7217. https://doi.org/10.1074/jbc.M411042200
Sacco T, Bruno A, Wanke E, Tempia F (2003) Functional roles of an ERG current isolated in cerebellar Purkinje neurons. J Neurophysiol 90:1817–1828. https://doi.org/10.1152/jn.00104.2003
Sanguinetti MC, Tristani-Firouzi M (2006) hERG potassium channels and cardiac arrhythmia. Nature 440:463–469. https://doi.org/10.1038/nature04710
Schonherr R et al (1999) Functional role of the slow activation property of ERG K+ channels. Eur J Neurosci 11:753–760
Schulze-Bahr E et al (1997) Autosomal recessive long-QT syndrome (Jervell Lange-Nielsen syndrome) is genetically heterogeneous. Hum Genet 100:573–576
Schwarz JR, Bauer CK (1999) The ether-a-go-go-related gene K(+) current: functions of a strange inward rectifier. News Physiol Sci 14:135–142
Shoeb F, Malykhina AP, Akbarali HI (2003) Cloning and functional characterization of the smooth muscle ether-a-go-go-related gene K+ channel—potential role of a conserved amino acid substitution in the S4 region. J Biol Chem 278:2503–2514. https://doi.org/10.1074/jbc.M208525200
Sturm P, Wimmers S, Schwarz JR, Bauer CK (2005) Extracellular potassium effects are conserved within the rat erg K+ channel family. J Physiol 564:329–345. https://doi.org/10.1113/jphysiol.2004.078840
Trudeau MC, Warmke JW, Ganetzky B, Robertson GA (1995) HERG, a human inward rectifier in the voltage-gated potassium channel family. Science 269:92–95
Vandenberg JI, Perry MD, Perrin MJ, Mann SA, Ke Y, Hill AP (2012) hERG K(+) channels: structure, function, and clinical significance. Physiol Rev 92:1393–1478
Vandenberg JI, Torres AM, Campbell TJ, Kuchel PW (2004) The HERG K+ channel: progress in understanding the molecular basis of its unusual gating kinetics. Eur Biophys J 33:89–97. https://doi.org/10.1007/s00249-003-0338-3
Wang J et al (2003) Functional and pharmacological properties of canine ERG potassium channels. Am J Physiol Heart Circ Physiol 284:H256–H267. https://doi.org/10.1152/ajpheart.00220.2002
Wu SH, Oertel D (1984) Intracellular injection with horseradish-peroxidase of physiologically characterized stellate and bushy cells in slices of mouse anteroventral cochlear nucleus. J Neurosci 4:1577–1588
Young ED, Oertel D (2004) Cochlear nucleus. In: Shepherd GM (ed) The synaptic organization of the brain, 5 edn. Oxford University Press, New York, pp 125–165
Acknowledgements
This work was supported by grants from Gaziantep University Scientific Research Projects Governing Unit (Project No.: TF.16.10) (Turkey). We thank Professor D. Ian Forsythe for his e-mail support to solve the problems.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Yildirim, C., Bal, R. ERG Channels Regulate Excitability in Stellate and Bushy Cells of Mice Ventral Cochlear Nucleus. J Membrane Biol 251, 711–722 (2018). https://doi.org/10.1007/s00232-018-0048-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00232-018-0048-5