Effectors of large-conductance calcium-activated potassium channel modulate glutamate excitotoxicity in organotypic hippocampal slice cultures

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Acta Neurobiologiae Experimentalis

Nencki Institute of Experimental Biology

Subject: Behavioral Sciences, Biomedical Sciences & Nutrition, Life Sciences, Medicine, Neurosciences

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eISSN: 1689-0035

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VOLUME 76 , ISSUE 1 (March 2016) > List of articles

Effectors of large-conductance calcium-activated potassium channel modulate glutamate excitotoxicity
in organotypic hippocampal slice cultures

Marta Piwońska / Adam Szewczyk / Ulrich H. Schröder / Klaus G. Reymann / Piotr Bednarczyk *

Keywords : potassium channel, glutamate, hippocampal slice cultures, mitochondria, respiration, patch-clamp

Citation Information : Acta Neurobiologiae Experimentalis. Volume 76, Issue 1, Pages 20-31, DOI: https://doi.org/10.21307/ane-2017-002

License : (CC BY 4.0)

Received Date : 29-October-2015 / Accepted: 07-January-2016 / Published Online: 14-August-2017

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ABSTRACT

Mitochondria have been suggested as a potential target for cytoprotective strategies. It has been shown that increased K+ uptake mediate by mitochondrial ATP-regulated potassium channels (mitoKATP channel) or large-conductance Ca2+-activated potassium channels (mitoBKCa channel) may provide protection in different models of cell death. Since recent findings demonstrated the presence of BKCa channels in neuronal mitochondria, the goal of the present study was to test the potential neuroprotective effects of BKCa channel modulators. Using organotypic hippocampal slice cultures exposed to glutamate, we demonstrated that preincubation of the slices with the BKCa channel opener NS1619 resulted in decreased neuronal cell death measured as reduced uptake of propidium iodide. This neuroprotective effect was reversed by preincubation with the BKCa channel inhibitors paxilline and Iberiotoxin (IbTx). Moreover, mitochondrial respiration
measurements revealed that NS1619 induced an IbTx-sensitive increase in state 2 respiration of isolated brain mitochondria. In addition,electrophysiological patch-clamp studies confirmed the presence of BKCa channels in mitoplasts isolated from embryonic hippocampal cells. Taken together, our results confirm presence of BKCa channel in rat hippocampal neurons mitochondria and suggest putative role for mitoBKCa in neuroprotection.

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REFERENCES

  1. Bednarczyk P, Kowalczyk JE, Beresewicz M, Dołowy K, Szewczyk A,Zabłocka B (2010) Identification of a voltage-gated potassium channel in gerbil hippocampal mitochondria. Biochem Biophys Res Commun 397: 614–620.
  2. Bednarczyk P, Koziel A, Jarmuszkiewicz W, Szewczyk A (2013a) Largeconductance Ca2+-activated potassium channel in mitochondria of endothelial EA.hy926 cells. Am J Physiol Heart Circ Physiol 304: H1415–H1427.
  3. Bednarczyk P, Wieckowski MR, Broszkiewicz M, Skowronek K, Siemen D,Szewczyk A (2013b) Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain. PLoS One 8:e68125.
  4. Busija DW, Gaspar T, Domoki F, Katakam PV, Bari F (2008) Mitochondrialmediated suppression of ROS production upon exposure of neurons to lethal stress: mitochondrial targeted preconditioning. Adv Drug Deliv Rev 60: 1471–1477.
  5. Cheney JA, Weisser JD, Bareyre FM, Laurer HL, Saatman KE, Raghupathi R,Gribkoff V, Starrett JE, McIntosh TK (2001) The Maxi-K channel opener BMS-204352 attenuates regional cerebral edema and neurologic motor
    impairment after experimental brain injury. J Cereb Blood Flow Metab 21: 396–403.
  6. Cheng Y, Gu XQ, Bednarczyk P, Wiedemann FR, Haddad GG, Siemen D (2008) Hypoxia increases activity of the BK-channel in the inner mitochondrial membrane and reduces activity of the permeability transition pore. Cell Physiol Biochem 22: 127–136.
  7. Debska G, Kicinska A, Dobrucki J, Dworakowska B, Nurowska E, Skalska J, Dołowy K, Szewczyk A (2003) Large-conductance K+ channel openers NS1619 and NS004 as inhibitors of mitochondrial function in glioma cells. Biochem Pharmacol 65: 1827–1834.
  8. Douglas RM, Lai JC, Bian S, Cummins L, Moczydlowski E, Haddad GG (2006) The calcium-sensitive large-conductance potassium channel (BK/MAXI K) is present in the inner mitochondrial membrane of rat brain.
    Neuroscience 139: 1249–1261.
  9. Eichhorn B, Dobrev D (2007) Vascular large conductance calcium-activated potassium channels: functional role and therapeutic potential. Naunyn Schmiedebergs Arch Pharmacol 376: 145–155.
  10. Facler B, Adelman JP (2008) Control of KCa channels by calcium nano/microdomains. Neuron 59: 873–881.
  11. Facundo HT, Fornazari M, Kowaltowski AJ (2006) Tissue protection mediated by mitochondrial K+ channels. Biochim Biophys Acta 1762: 202–212.
  12. Fahnik-Babaei J, Eliassi A, Jafari A, Sauve R, Salari S, Saghiri R (2011) Electro-pharmacological profile of a mitochondrial inner membrane big-potassium channel from rat brain. Biochim Biophys Acta 1808:454–460.
  13. Feissner RF, Skalska J, Gaum WE, Sheu SS (2009) Crosstalk signaling between mitochondrial Ca2+ and ROS. Front Biosci 14: 1197–1218.
  14. Gaspar T, Katakam P, Snipes JA, Kis B, Domoki F, Bari F, Busija DW (2008a) Delayed neuronal preconditioning by NS1619 is independent of calcium activated potassium channels. J Neurochem 105: 1115–1128.
  15. Gaspar T, Snipes JA, Busija AR, Kis B, Domoki F, Bari F, Busija DW (2008b) ROS-independent preconditioning in neurons via activation of mitoKATP channels by BMS-191095. J Cereb Blood Flow Metab 28: 1090–1103.
  16. Gribkoff VK, Starrett Jr JE, Dworetzky SI, Hewawasam P, Boissard CG, Cook DA, Frantz, SW, Heman K, Hibbard JR, Huston K, Johnson G, Krishnan BS, Kinney GG, Lombardo LA, Meanwell NA, Molinoff PB, Myers RA, Moon SL, Ortiz A, Pajor L, Pieschl RL, Post-Munson DJ, Signor LJ, Srinivas N, Taber MT, Thalody G, Trojnacki JT, Wiener H, Yeleswaram K, Yeola SW (2001) Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels. Nat Med 7: 471–477.
  17. Grimm PR, Sansom SC (2007) BK channels in the kidney. Curr Opin Nephrol Hypertens 16: 430–436.
  18. Grover GJ, D’Alonzo AJ, Garlid KD, Bajgar R, Lodge NJ, Sleph PG, Darbenzio RB, Hess TA, Smith MA, Paucek P, Atwal KS (2001) Pharmacologic characterization of BMS-191095, a mitochondrial K(ATP) opener with no peripheral vasodilator or cardiac action potential shortening activity. J Pharmacol Exp Ther 297: 1184–1192.
  19. Halestrap AP, Clarke SJ, Khaliulin I (2007) The role of mitochondria in protection of the heart by preconditioning. Biochim Biophys Acta 1767:1007–1031.
  20. Heinen A, Aldakkak M, Stowe DF, Rhodes SS, Riess ML, Varadarajan SG, Camara AK (2007a) Reverse electron flow-induced ROS production is attenuated by activation of mitochondrial Ca2+-sensitive K+ channels. Am J Physiol Heart Circ Physiol 293: H1400–H1407.
  21. Heinen A, Camara AK, Aldakkak M, Rhodes SS, Riess ML, Stowe DF (2007b) Mitochondrial Ca2+-induced K+ influx increases respiration and enhances ROS production while maintaining membrane potential. Am J Physiol
    Cell Physiol 292: C148–C156.
  22. Hu H, Sato T, Seharaseyon J, Liu Y, Johns DC, O’Rourke B, Marbán E (1999) Pharmacological and histochemical distinctions between molecularly defined sarcolemmal KATP channels and native cardiac mitochondrial KATP channels. Mol Pharmacol 55: 1000–1005.
  23. Kicinska A, Szewczyk A (2004) Large-conductance potassium cation channel opener NS1619 inhibits cardiac mitochondria respiratory chain. Toxicol Mech Methods 14: 59–61.
  24. Kis B, Nagy K, Snipes JA, Rajapakse NC, Horiguchi T, Grover GJ, Busija DW (2004) The mitochondrial KATP channel opener BMS-191095 induces neuronal preconditioning. Neuroreport 15: 345–349.
  25. Kis B, Rajapakse NC, Snipes JA, Nagy K, Horiguchi T, Busija DW (2003) Diazoxide induces delayed pre-conditioning in cultured rat cortical neurons. J Neurochem 87: 969–980.
  26. Kulawiak B, Kunin AP, Szewczyk A, Kunz WS (2008) BK channel openers inhibit ROS production of isolated rat brain mitochondria. Exp Neurol 212: 543–547.
  27. Latorre R, Brauchi S (2006) Large conductance Ca2+-activated K+ (BK) channel: activation by Ca2+ and voltage. Biol Res 39: 385–401.
  28. Ljubkovic M, Marinovic J, Fuchs A, Bosnjak ZJ, Bienengraeber M (2006) Targeted expression of Kir6.2 in mitochondria confers protection against hypoxic stress. J Physiol 577: 17–29.
  29. Mayanagi K, Gáspár T, Katakam PV, Kis B, Busija DW (2007) The mitochondrial KATP channel opener BMS-191095 reduces neuronal damage after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab 27: 348–355.
  30. Munoz A, Nakazaki M, Goodman JC, Barrios R, Onetti CG, Bryan J, Aguilar-Bryan L (2003) Ischemic preconditioning in the hippocampus of a knockout mouse lacking SUR1-based KATP channels. Stroke 34: 164–170.
  31. Murphy E, Steenbergen C (2007) Preconditioning: The mitochondrial connection. Annu Rev Physiol 69: 51–67.
  32. Nagy K, Kis B, Rajapakse NC, Bari F, Busija DW (2004) Diazoxide preconditioning protects against neuronal cell death by attenuation of oxidative stress upon glutamate stimulation. J Neurosci Res 76:697–704.
  33. Nieminen AL, Petrie TG, Lemasters JJ, Selman WR (1996) Cyclosporin A delays mitochondrial depolarization induced by N-methyl-D-aspartate in cortical neurons: evidence of the mitochondrial permeability transition. Neuroscience 75: 993–997.
  34. O’Rourke B (2007) Mitochondrial ion channels. Annu Rev Physiol 69: 19–49.
  35. Pivovarova NB, Stanika RI, Watts CA, Brantner CA, Smith CL, Andrews SB (2008) Reduced calcium-dependent mitochondrial damage underlies the reduced vulnerability of excitotoxicity-tolerant hippocampal
    neurons. J Neurochem 104: 1686–1699.
  36. Piwonska M, Wilczek E, Szewczyk A, Wilczyński GM (2008) Differential distribution of Ca2+-activated potassium channel β4 subunit in rat brain: immunolocalization in neuronal mitochondria. Neuroscience
    153: 446–460.
  37. Raval AP, Dave KR, DeFazio RA, Perez-Pinzon MA (2007) EpsilonPKC phosphorylates the mitochondrial K+ ATP channel during induction of ischemic preconditioning in the rat hippocampus. Brain Res 1184:
    345–353.
  38. Rodriguez-Pallares J, Parga JA, Joglar B, Guerra MJ, Labandeira-Garcia JL (2009) The mitochondrial ATP-sensitive potassium channel blocker 5-hydroxydecanoate inhibits toxicity of 6-hydroxydopamine on
    dopaminergic neurons. Neurotox Res 15: 82–95.
  39. Sato T, Saito T, Saegusa N, Nakaya H (2005) Mitochondrial Ca2+-activated K+ channels in cardiac myocytes: a mechanism of the cardioprotective effect and modulation by protein kinase A. Circulation 111: 198–203.
  40. Siemen D, Loupatatzis C, Borecky J, Gulbins E, Lang F (1999) Ca2+-activated K channel of the BK-type in the inner mitochondrial membrane of a human glioma cell line. Biochem Biophys Res Commun 257: 549–554.
  41. Skalska J, Bednarczyk P, Piwonska M, Kulawiak B, Wilczynski G, Dolowy K, Kudin AP, Kunz WS, Szewczyk A (2009) Calcium ions regulate K uptake into brain mitochondria: the evidence for a novel potassium channel. Int
    J Mol Sci 10: 1104–1120.
  42. Skalska J, Piwonska M, Wyroba E, Surmacz L, Wieczorek R, Koszela-Piotrowska I, Zielinska J, Bednarczyk P, Dolowy K, Wilczynski GM, Szewczyk A, Kunz WS (2008) A novel potassium channel in skeletal muscle mitochondria. Biochim Biophys Acta 1777: 651–659.
  43. Stoppini L, Buchs PA, Muller D (1991) A simple method for organotypic cultures of nervous tissue. J Neurosci Methods 37: 173–182.
  44. Stout AK, Raphael HM, Kanterewicz BI, Klann E, Reynolds IJ (1998) Glutamate-induced neuron death requires mitochondrial calcium uptake. Nat Neurosci 1: 366–373.
  45. Szabo I, Zoratti M (2014) Mitochondrial channels: ion fluxes and more. Physiol Rev 94: 519–608.
  46. Szewczyk A, Jarmuszkiewicz W, Kunz WS (2009) Mitochondrial potassium channels. IUBMB Life 61: 134–143.
  47. Szewczyk A, Kajma A, Malinska D, Wrzosek A, Bednarczyk P, Zablocka B, Dolowy K (2010) Pharmacology of mitochondrial potassium channels: dark side of the field. FEBS Lett 584: 2063–2069.
  48. Szewczyk A, Marban E (1999) Mitochondria: a new target for K channel openers?. Trends Pharmacol Sci 20: 157–161.
  49. Watanabe M, Katsura K, Ohsawa I, Mizukoshi G, Takahashi K, Asoh S, Ohta S, Katayama Y (2008) Involvement of mitoKATP channel in protective mechanisms of cerebral ischemic tolerance. Brain Res 1238: 199–207.
  50. White RJ, Reynolds IJ (1996) Mitochondrial depolarization in glutamatestimulated neurons: an early signal specific to excitotoxin exposure. J Neurosci 16: 5688–5697.
  51. Xu W, Liu Y, Wang S, McDonald T, Van Eyk JE, Sidor A, O’Rourke B (2002) Cytoprotective role of Ca2+-activated K+ channels in the cardiac inner mitochondrial membrane. Science 298: 1029–1033.

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