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Modulation of Excitability of Stellate Neurons in the Ventral Cochlear Nucleus of Mice by ATP-Sensitive Potassium Channels

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Abstract

Major voltage-activated ionic channels of stellate cells in the ventral part of cochlear nucleus (CN) were largely characterized previously. However, it is not known if these cells are equipped with other ion channels apart from the voltage-sensitive ones. In the current study, it was aimed to study subunit composition and function of ATP-sensitive potassium channels (KATP) in stellate cells of the ventral cochlear nucleus. Subunits of KATP channels, Kir6.1, Kir6.2, SUR1, and SUR2, were expressed at the mRNA level and at the protein level in the mouse VCN tissue. The specific and clearly visible bands for all subunits but that for Kir6.1 were seen in Western blot. Using immunohistochemical staining technique, stellate cells were strongly labeled with SUR1 and Kir6.2 antibodies and moderately labeled with SUR2 antibody, whereas the labeling signals for Kir6.1 were too weak. In patch clamp recordings, KATP agonists including cromakalim (50 µM), diazoxide (0.2 mM), 3-Amino-1,2,4-triazole (ATZ) (1 mM), 2,2-Dithiobis (5-nitro pyridine) (DTNP) (330 µM), 6-Chloro-3-isopropylamino- 4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NNC 55-0118) (1 µM), 6-chloro-3-(methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NN414) (1 µM), and H2O2 (0.88 mM) induced marked responses in stellate cells, characterized by membrane hyperpolarization which were blocked by KATP antagonists. Blockers of KATP channels, glibenclamide (0.2 mM), tolbutamide (0.1 mM) as well as 5-hydroxydecanoic acid (1 mM), and catalase (500 IU/ml) caused depolarization of stellate cells, increasing spontaneous action potential firing. In conclusion, KATP channels seemed to be composed dominantly of Kir 6.2 subunit and SUR1 and SUR2 and activation or inhibition of KATP channels regulates firing properties of stellate cells by means of influencing resting membrane potential and input resistance.

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References

  • Adams JC, Warr WB (1976) Origins of axons in the cat’s acoustic striae determined by injection of horseradish peroxidase into severed tracts. Comp Neurol 170:107–121

    Article  CAS  Google Scholar 

  • Aguilar-Bryan L, Clement JP, Gonzalez G, Kunjilwar K, Babenko A, Bryan J (1998) Toward understanding the assembly and structure of KATP channels. Physiol Rev 78:227–245

    Article  CAS  PubMed  Google Scholar 

  • Allen TG, Brown DA (2004) Modulation of the excitability of cholinergic basal forebrain neurones by KATP channels. J Physiol 554:353–370

    Article  CAS  PubMed  Google Scholar 

  • Ashcroft FM, Gribble FM (1998) Correlating structure and function in ATP-sensitive K+ channels. Trends Neurosci 21:288–294

    Article  CAS  PubMed  Google Scholar 

  • Ashcroft SJ, Ashcroft FM (1990a) Properties and functions of ATP-sensitive K-channels. Cell Signal 2:197–214

    Article  CAS  PubMed  Google Scholar 

  • Ashcroft SJ, Ashcroft FM (1990b) Properties and functions of ATP-sensitive K-channels. Cell Signal 2:197–214

    Article  CAS  PubMed  Google Scholar 

  • Ashford ML, Boden PR, Treherne JM (1990a) Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K+ channels. Pflugers Arch 415:479–483

    Article  CAS  PubMed  Google Scholar 

  • Ashford ML, Boden PR, Treherne JM (1990b) Tolbutamide excites rat glucoreceptive ventromedial hypothalamic neurones by indirect inhibition of ATP-K+ channels. Br J Pharmacol 101:531–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Avshalumov MV, Chen BT, Koos T, Tepper JM, Rice ME (2005) Endogenous hydrogen peroxide regulates the excitability of midbrain dopamine neurons via ATP-sensitive potassium channels. J Neurosci 25:4222–4231

  • Babenko AP, Gonzalez G, Bryan J (2000) Pharmaco-topology of sulfonylurea receptors. Separate domains of the regulatory subunits of K(ATP) channel isoforms are required for selective interaction with K(+) channel openers. J Biol Chem 275:717–720

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Bal R, Baydas G, Naziroglu M (2009) Electrophysiological properties of ventral cochlear nucleus neurons of the dog. Hear Res 256:93–103

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Bal R, Oertel D (2001) Potassium currents in octopus cells of the mammalian cochlear nucleus. J Neurophysiol 86:2299–2311

    Article  CAS  PubMed  Google Scholar 

  • Bal R, Oertel D (2007) Voltage-activated calcium currents in octopus cells of the mouse cochlear nucleus. J Assoc Res Otolaryngol 8:509–521

    Article  PubMed  PubMed Central  Google Scholar 

  • Balfour RH, Hansen AM, Trapp S (2006) Neuronal responses to transient hypoglycaemia in the dorsal vagal complex of the rat brainstem. J Physiol 570:469–484

    Article  CAS  PubMed  Google Scholar 

  • Bao L, Taskin E, Foster M, Ray B, Rosario R, Ananthakrishnan R, Howlett SE, Schmidt AM, Ramasamy R, Coetzee WA (2013) Alterations in ventricular K(ATP) channel properties during aging. Aging Cell 12:167–176

    Article  CAS  PubMed  Google Scholar 

  • Baukrowitz T, Schulte U, Oliver D, Herlitze S, Krauter T, Tucker SJ, Ruppersberg JP, Fakler B (1998) PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science 282:1141–1144

    Article  CAS  PubMed  Google Scholar 

  • Brawer JR, Morest DK (1975) Relations between auditory nerve endings and cell types in the cat’s anteroventral cochlear nucleus seen with the Golgi method and Nomarski optics. J Comp Neurol 160:491–506

    Article  CAS  PubMed  Google Scholar 

  • Bustamante JO (2006) Current concepts in nuclear pore electrophysiology. Can J Physiol Pharmacol 84:347–365

    Article  CAS  PubMed  Google Scholar 

  • Calabrese V, Cornelius C, Maiolino L, Luca M, Chiaramonte R, Toscano MA, Serra A (2010) Oxidative stress, redox homeostasis and cellular stress response in Meniere’s disease: role of vitagenes. Neurochem Res 35:2208–2217

    Article  CAS  PubMed  Google Scholar 

  • Cao XJ, Shatadal S, Oertel D (2007) Voltage-sensitive conductances of bushy cells of the Mammalian ventral cochlear nucleus. J Neurophysiol 97:3961–3975

    Article  PubMed  Google Scholar 

  • Capaccio P, Pignataro L, Gaini LM, Sigismund PE, Novembrino C, De Giuseppe R, Uva V, Tripodi A, Bamonti F (2011) Unbalanced oxidative status in idiopathic sudden sensorineural hearing loss. Eur Arch Otorhinolaryngol 269:449–453

    Article  PubMed  Google Scholar 

  • Carr RD, Brand CL, Bodvarsdottir TB, Hansen JB, Sturis J (2003) NN414, a SUR1/Kir6.2-selective potassium channel opener, reduces blood glucose and improves glucose tolerance in the VDF Zucker rat. Diabetes 52:2513–2518

    Article  CAS  PubMed  Google Scholar 

  • Clark R, Proks P (2010) ATP-sensitive potassium channels in health and disease. Adv Exp Med Biol 654:165–192

    Article  CAS  PubMed  Google Scholar 

  • Cohen G (1994) Enzymatic/nonenzymatic sources of oxyradicals and regulation of antioxidant defenses. Ann N Y Acad Sci 738:8–14

    Article  CAS  PubMed  Google Scholar 

  • Dabrowski M, Larsen T, Ashcroft FM, Bondo Hansen J, Wahl P (2003) Potent and selective activation of the pancreatic beta-cell type K(ATP) channel by two novel diazoxide analogues. Diabetologia 46:1375–1382

    Article  CAS  PubMed  Google Scholar 

  • Dunn-Meynell AA, Rawson NE, Levin BE (1998) Distribution and phenotype of neurons containing the ATP-sensitive K+ channel in rat brain. Brain Res 814:41–54

    Article  CAS  PubMed  Google Scholar 

  • Fechter LD (2005) Oxidative stress: a potential basis for potentiation of noise-induced hearing loss. Environ Toxicol Pharmacol 19:543–546

    Article  CAS  PubMed  Google Scholar 

  • Fellows LK, Boutelle MG, Fillenz M (1993) ATP-sensitive potassium channels and local energy demands in the rat hippocampus: an in vivo study. J Neurochem 61:949–954

    Article  CAS  PubMed  Google Scholar 

  • Ferragamo MJ, Golding NL, Oertel D (1998) Synaptic inputs to stellate cells in the ventral cochlear nucleus. J Neurophysiol 79:51–63

    Article  CAS  PubMed  Google Scholar 

  • Fridovich I (1995) Superoxide radical and superoxide dismutases. Annu Rev Biochem 64:97–112

    Article  CAS  PubMed  Google Scholar 

  • Golding NL, Ferragamo MJ, Oertel D (1999) Role of intrinsic conductances underlying responses to transients in octopus cells of the cochlear nucleus. J Neurosci 19:2897–2905

    CAS  PubMed  Google Scholar 

  • Golding NL, Robertson D, Oertel D (1995) Recordings from slices indicate that octopus cells of the cochlear nucleus detect coincident firing of auditory nerve fibers with temporal precision. J Neurosci 15:3138–3153

    CAS  PubMed  Google Scholar 

  • Gribble FM, Ashcroft FM (2000) Sulfonylurea sensitivity of adenosine triphosphate-sensitive potassium channels from beta cells and extrapancreatic tissues. Metabolism 49:3–6

    Article  CAS  PubMed  Google Scholar 

  • Harrison JM, Irving R (1966) The organization of the posterior ventral cochlear nucleus in the rat. J Comp Neurol 126:391–401

    Article  CAS  PubMed  Google Scholar 

  • Inagaki N, Gonoi T, Clement JP, Wang CZ, Aguilar-Bryan L, Bryan J, Seino S (1996) A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels. Neuron 16:1011–1017

    Article  CAS  PubMed  Google Scholar 

  • Inagaki N, Tsuura Y, Namba N, Masuda K, Gonoi T, Horie M, Seino Y, Mizuta M, Seino S (1995) Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J Biol Chem 270:5691–5694

    Article  CAS  PubMed  Google Scholar 

  • Karschin A, Brockhaus J, Ballanyi K (1998) KATP channel formation by the sulphonylurea receptors SUR1 with Kir6.2 subunits in rat dorsal vagal neurons in situ. J Physiol 509(Pt 2):339–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karschin C, Ecke C, Ashcroft FM, Karschin A (1997) Overlapping distribution of K(ATP) channel-forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain. FEBS Lett 401:59–64

    Article  CAS  PubMed  Google Scholar 

  • Kossl M, Vater M (1989) Noradrenaline enhances temporal auditory contrast and neuronal timing precision in the cochlear nucleus of the mustached bat. J Neurosci 9:4169–4178

    CAS  PubMed  Google Scholar 

  • Lamm K, Arnold W (1996) Noise-induced cochlear hypoxia is intensity dependent, correlates with hearing loss and precedes reduction of cochlear blood flow. Audiol Neurootol 1:148–160

    Article  CAS  PubMed  Google Scholar 

  • Lee K, Brownhill V, Richardson PJ (1997) Antidiabetic sulphonylureas stimulate acetylcholine release from striatal cholinergic interneurones through inhibition of K(ATP) channel activity. J Neurochem 69:1774–1776

    Article  CAS  PubMed  Google Scholar 

  • Lee K, Dixon AK, Freeman TC, Richardson PJ (1998) Identification of an ATP-sensitive potassium channel current in rat striatal cholinergic interneurones. J Physiol 510(Pt 2):441–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee K, Dixon AK, Richardson PJ, Pinnock RD (1999) Glucose-receptive neurones in the rat ventromedial hypothalamus express KATP channels composed of Kir6.1 and SUR1 subunits. J Physiol 515(Pt 2):439–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liss B, Roeper J (2001) Molecular physiology of neuronal K-ATP channels (review). Mol Membr Biol 18:117–127

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Seino S, Kirchgessner AL (1999) Identification and characterization of glucoresponsive neurons in the enteric nervous system. J Neurosci 19:10305–10317

    CAS  PubMed  Google Scholar 

  • Matsumoto N, Komiyama S, Akaike N (2002) Pre- and postsynaptic ATP-sensitive potassium channels during metabolic inhibition of rat hippocampal CA1 neurons. J Physiol 541:511–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mattson MP, Duan W, Pedersen WA, Culmsee C (2001) Neurodegenerative disorders and ischemic brain diseases. Apoptosis 6:69–81

    Article  CAS  PubMed  Google Scholar 

  • Miki T, Liss B, Minami K, Shiuchi T, Saraya A, Kashima Y, Horiuchi M, Ashcroft F, Minokoshi Y, Roeper J, Seino S (2001) ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis. Nat Neurosci 4:507–512

    Article  CAS  PubMed  Google Scholar 

  • Needham K, Paolini AG (2003) Fast inhibition underlies the transmission of auditory information between cochlear nuclei. J Neurosci 23:6357–6361

    CAS  PubMed  Google Scholar 

  • Nichols CG (2006) KATP channels as molecular sensors of cellular metabolism. Nature 440:470–476

    Article  CAS  PubMed  Google Scholar 

  • Nielsen FE, Bodvarsdottir TB, Worsaae A, MacKay P, Stidsen CE, Boonen HC, Pridal L, Arkhammar PO, Wahl P, Ynddal L, Junager F, Dragsted N, Tagmose TM, Mogensen JP, Koch A, Treppendahl SP, Hansen JB (2002) 6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives potently and selectively activate ATP sensitive potassium channels of pancreatic beta-cells. J Med Chem 45:4171–4187

    Article  CAS  PubMed  Google Scholar 

  • Noma A (1983) ATP-regulated K+ channels in cardiac muscle. Nature 305:147–148

    Article  CAS  PubMed  Google Scholar 

  • Oertel D (1991) The role of intrinsic neuronal properties in the encoding of auditory information in the cochlear nuclei. Curr Opin Neurobiol 1:221–228

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Osen KK (1970) Course and termination of the primary afferents in the cochlear nuclei of the cat. An experimental anatomical study. Arch italiennes deBiol 108:21–51

    CAS  Google Scholar 

  • Osen KK (1972) Projection of the cochlear nuclei on the inferior colliculus in the cat. J Comp Neurol 144:355–372

    Article  CAS  PubMed  Google Scholar 

  • Pierrefiche O, Bischoff AM, Richter DW (1996) ATP-sensitive K+ channels are functional in expiratory neurones of normoxic cats. J Physiol 494(Pt 2):399–409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodrigues AR, Oertel D (2006) Hyperpolarization-activated currents regulate excitability in stellate cells of the mammalian ventral cochlear nucleus. J Neurophysiol 95:76–87

    Article  PubMed  Google Scholar 

  • Smith PH, Rhode WS (1989) Structural and functional properties distinguish two types of multipolar cells in the ventral cochlear nucleus. J Comp Neurol 282:595–616

    Article  CAS  PubMed  Google Scholar 

  • Stanford IM, Lacey MG (1995) Regulation of a potassium conductance in rat midbrain dopamine neurons by intracellular adenosine triphosphate (ATP) and the sulfonylureas tolbutamide and glibenclamide. J Neurosci 15:4651–4657

    CAS  PubMed  Google Scholar 

  • Thomzig A, Wenzel M, Karschin C, Eaton MJ, Skatchkov SN, Karschin A, Veh RW (2001) Kir6.1 is the principal pore-forming subunit of astrocyte but not neuronal plasma membrane K-ATP channels. Mol Cell Neurosci 18:671–690

    Article  CAS  PubMed  Google Scholar 

  • Tokube K, Kiyosue T, Arita M (1998) Effects of hydroxyl radicals on KATP channels in guinea-pig ventricular myocytes. Pflugers Arch 437:155–157

    Article  CAS  PubMed  Google Scholar 

  • Trapp S, Ballanyi K, Richter DW (1994) Spontaneous activation of KATP current in rat dorsal vagal neurones. Neuroreport 5:1285–1288

    Article  CAS  PubMed  Google Scholar 

  • Yamane H, Nakai Y, Takayama M, Iguchi H, Nakagawa T, Kojima A (1995) Appearance of free radicals in the guinea pig inner ear after noise-induced acoustic trauma. Eur Arch Otorhinolaryngol 252:504–508

    Article  CAS  PubMed  Google Scholar 

  • Zawar C, Plant TD, Schirra C, Konnerth A, Neumcke B (1999) Cell-type specific expression of ATP-sensitive potassium channels in the rat hippocampus. J Physiol 514(Pt 2):327–341

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou M, Tanaka O, Sekiguchi M, Sakabe K, Anzai M, Izumida I, Inoue T, Kawahara K, Abe H (1999) Localization of the ATP-sensitive potassium channel subunit (Kir6. 1/uK(ATP)-1) in rat brain. Mol Brain Res 74:15–25

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Grants from TUBITAK, 109S516 and 110S397 (Turkey). We thank Novo Nordisk A/S (Novo Nordisk, Bagsvaerd, Denmark) for providing NNC 55-0118 and NN414.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Gaziantep University, 27310, Gaziantep, Turkey

    Ramazan Bal & Caner Yildirim

  2. Department of Physiology, Faculty of Medicine, Medipol University, Istanbul, Turkey

    Gurkan Ozturk

  3. Department of Medical Biology, Firat University, 23119, Elazig, Turkey

    Ebru Onalan Etem & Ahmet Tektemur

  4. Department of Biophysics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey

    Aydin Him

  5. Department of Histology and Embryology, Faculty of Medicine, Sakarya University, 23119, Sakarya, Turkey

    Nurattin Cengiz

  6. Department of Histology and Embryology, Faculty of Medicine, Firat University, 23119, Elazig, Turkey

    Tuncay Kuloglu

  7. Department of Biology, Faculty of Science, Firat University, 23119, Elazig, Turkey

    Mehmet Tuzcu

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  1. Ramazan Bal
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Bal, R., Ozturk, G., Etem, E.O. et al. Modulation of Excitability of Stellate Neurons in the Ventral Cochlear Nucleus of Mice by ATP-Sensitive Potassium Channels. J Membrane Biol 251, 163–178 (2018). https://doi.org/10.1007/s00232-017-0011-x

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