Biophysical Properties of ERG Channels in Octopus Neurons of Ventral Cochlear Nucleus

Caner Yıldırım; Ramazan Bal

doi:10.5152/EurJTher.2018.875

Authors

Caner Yıldırım Department of Physiology, Gaziantep University School of Medicine, Gaziantep https://orcid.org/0000-0003-0091-9925
Ramazan Bal Department of Physiology, Gaziantep University School of Medicine, Gaziantep https://orcid.org/0000-0003-3829-8669

DOI:

https://doi.org/10.5152/EurJTher.2018.875

Keywords:

Auditory pathway, cochlear nucleus, electrophysiology, ERG channels, patch clamp

Abstract

Objective: ERG (Ether a go go related gene) channels (Kv 11) are the members of the voltage-dependent potassium channel family, which have three subtypes as ERG1 (Kv 11.1), ERG2 (Kv 11.2), ERG3 (Kv 11.3). Electrophysiological, biophysical properties of ERG channels and their functions are not known in the cochlear nucleus (CN) neurons, which is the first relay station of auditory pathway. For that reason, we aimed to study pharmacological and biophysical properties and their functions in the octopus neurons of the ventral cochlear nucleus (VCN).
Methods: A total of 70 mice at 14-17 day-old were used for this study. Electrophysiological characterization of ERG channels was performed using patch clamp technique in CN slices.
Results: In current clamp, application of ERG channel blockers, terfenadine (10 μM) and E-4031 (10 μM), significantly increased input resistance in all the cells (p<0.05). Also, in octopus cells, it was found that terfenadine (10 μM) and E-4031 (10 μM) significantly reduced threshold for induction of action potentials (AP) with square current pulses (p<0.05). Tail ERG currents were measured under voltage-clamp. Steady state activation curve for ERG tail current was determined, yielding a half-activation voltage (V0.5) and slope factor (k factor). Steady state activation curve for ERG tail current was determined with a half-activation voltage in Octopus cell V0.5 -50.72±0.32 with a slope factor of 6.04±0.23 mV (n=3). The quasy steady-state inactivation curve for chord conductances gave for Octopus cell V0.5 value of -74.34±0.46 and the slope of 7.89±0.32 (n=3).
Conclusion: In conclusion, the findings obtained in the present study suggest that Octopus neurons express ERG channels and appear to threshold for AP induction and, possibly, resting membrane potentials in this cells.

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References

Vandenberg JI, Perry MD, Perrin MJ, Mann SA, Ke Y, Hill AP. hERG K(+) channels: structure, function, and clinical significance. Physiol Rev 2012; 92: 1393-478.

Rampe D, Brown AM. A history of the role of the hERG channel in cardiac risk assessment. J Pharmacol Toxicol Methods 2013; 68: 13-22.

Heo DH, Kang TC. The changes of ERG channel expression after administration of antiepileptic drugs in the hippocampus of epilepsy gerbil model. Neurosci Lett 2012; 507: 27-32.

Bal R, Baydas G. Electrophysiological properties of octopus neurons of the cat cochlear nucleus: an in vitro study. J Assoc Res Otolaryngol 2009; 10: 281-93.

Oertel D, Wright S, Cao XJ, Ferragamo M, Bal R. The multiple functions of T stellate/multipolar/chopper cells in the ventral cochlear nucleus. Hear Res 2011; 276: 61-9.

Willott JF, Bross LS. Morphology of the Octopus Cell Area of the Cochlear Nucleus in Young and Aging C57bl/6j and Cba/J Mice. J Comp Neurol 1990; 300: 61-81.

Bal R, Ozturk G, Etem EO, Him A, Cengiz N, Kuloglu T, et al. Modulation of Excitability of Stellate Neurons in the Ventral Cochlear Nucleus of Mice by ATP-Sensitive Potassium Channels. J Membr Biol 2018; 251: 163-78.

Yildirim C, Bal R. ERG Channels Regulate Excitability in Stellate and Bushy Cells of Mice Ventral Cochlear Nucleus. J Membr Biol 2018; 251: 711-22.

Hardman RM, Forsythe ID. Ether-a-go-go-related gene K+ channels contribute to threshold excitability of mouse auditory brainstem neurons. J Physiol 2009; 587: 2487-97.

Pessia M, Servettini I, Panichi R, Guasti L, Grassi S, Arcangeli A, et al. ERG voltage-gated K+ channels regulate excitability and discharge dynamics of the medial vestibular nucleus neurones. J Physiol 2008; 586: 4877-90.

Sacco T, Bruno A, Wanke E, Tempia F. Functional roles of an ERG current isolated in cerebellar Purkinje neurons. J Neurophysiol 2003;90: 1817-28.

Niculescu D, Hirdes W, Hornig S, Pongs O, Schwarz JR. Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation. J Neurosci 2013; 33:16729-40.

Shibasaki T. Conductance and kinetics of delayed rectifier potassium channels in nodal cells of the rabbit heart. J Physiol 1987; 387:227-50.

Shoeb F, Malykhina AP, Akbarali HI. 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 2003; 278: 2503-14.

Smith PL, Baukrowitz T, Yellen G. The inward rectification mechanism of the HERG cardiac potassium channel. Nature 1996; 379: 833-6.

Ohya S, Horowitz B, Greenwood IA. Functional and molecular identification of ERG channels in murine portal vein myocytes. Am J Physiol Cell Physiol 2002; 283: C866-77.