Differential Changes of ATP-sensitive Potassium Channel Current after Hypoxia-reperfusion Treatment in Mouse Neuroblastoma 2a (N2a) Cell

  • Park, Ji-Ho (Department of Neuroscience, Graduate School of East-West Medical Science, Kyung Hee University)
  • Published : 2002.08.21

Abstract

Ischemic damage is one of the most serious problems. The openers of KATP channel have been suggested to have an effect to limit the ischemic damage. However, it is not yet clear how KATP channels of a cell correspond to hypoxic damage. To address the question, N2a cells were exposed to two different hypoxic conditions as follows: 6 hours hypoxia followed by 3 hours reperfusion and 12 hours hypoxia followed by 3 hours reperfusion. As the results, 6 hours hypoxic treatment increased glibenclamide- sensitive basal $K_{ATP}$ current activity (approximately 6.5-fold at 0 mV test potential) when compared with nomoxic condition. In contrast, 12 hours hypoxic treatment induced a relatively smaller change in the $K_{ATP}$ current density (2.5-fold at 0 mV test potential). Additionally, in experiments where $K_{ATP}$ channels were opened using diazoxide, the hypoxia for 6 hours significantly increased the current density in comparison to control condition (p<0.001). Interestingly, the augmentation in the $K_{ATP}$ current density reduced after exposure to the 12 hours hypoxic condition (p<0.001). Taken together, these results suggest that $K_{ATP}$ channels appear to be recruited more in cells exposed to the 6 hours hypoxic condition and they may play a protective role against hypoxia-reperfusion damage within the time range.

Keywords

References

  1. Abele A, Miller R. Potassium channel activators abolish excitotoxicity in cultured hippocampal pyramidal neurons. Neurosci Lett 115: 195-200, 1990 https://doi.org/10.1016/0304-3940(90)90454-H
  2. Ashcroft FM, Rorsman P. ATP-sensitive K$^+$channels: a link between B-cell metabolism and insulin secretion. Biochem Soc Trans 18(1): 109-111, 1990 https://doi.org/10.1042/bst0180109
  3. Ashocroft AJ, Ashocroft FM. Properties and functions of ATPsensitive K-channel. Cell Signal 2: 197-214, 1990 https://doi.org/10.1016/0898-6568(90)90048-F
  4. Bartus RT, Baker KL, Heiser AD, Sawyer SD, Dean RL, Elliott PJ, Straub JA. Postischemic administration of AK275, a calpain inhibitor, provides substantial protection against focal ischemic brain damage. J Cereb Blood Flow Metab 14: 537-544, 1994 https://doi.org/10.1038/jcbfm.1994.67
  5. Belousov AB, Godfraind JM, Krnjevic K. Internal Ca$^2+$ stores involved in anoxic responses of rat hippocampal neurons. J Physiol 486(Pt 3): 547-556, 1995 https://doi.org/10.1113/jphysiol.1995.sp020833
  6. Ben-Ari Y, Krnjevic K, Crepel V. Activators of ATP-sensitive K+ channels reduce anoxic depolarization in CA3 hippocampal neurons. Neuroscience 37: 55-60, 1990 https://doi.org/10.1016/0306-4522(90)90191-6
  7. Bray K, Quast U. Differential inhibition by tedisamil (KC8857) and glibenclamide of the responses to cromakalim and minoxidil sulphate in rat isolated aorta. Naunyn Schmiedebergs Arch Pharmacol 345: 244-250, 1992 https://doi.org/10.1007/BF00165744
  8. Chi XX, Xu ZC. Differential changes of potassium currents in CA1 pyramidal neurons after transient forebrain ischemia. J Neurophysiol Dec 84(6): 2834-2843, 2000 https://doi.org/10.1152/jn.2000.84.6.2834
  9. Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron 1: 623-634, 1988 https://doi.org/10.1016/0896-6273(88)90162-6
  10. Edwards G, Weston AH. The pharmacology of ATP-sensitive potassium channels. Annu Rev Pharmacol Toxicol 33: 597-637, 1993 https://doi.org/10.1146/annurev.pa.33.040193.003121
  11. Grover GJ, D'Alonzo AJ, Hess T, Sleph PG, Darbenzio RB. Glyburide- reversible cardioprotective effect of BMS-180448 is independent of action potential shortening. Cardiovasc Res 30(5): 731-738, 1995 https://doi.org/10.1016/S0008-6363(95)00102-6
  12. Heurteaux C, Bertaina V, Widmann C, Lazdunski M. K$^+$channel openers prevent global ischemia-induced expression of c-fos, c-jun, heat shock protein, and amyloid b-protein precursor genes and heat shock protein, and amyloid-protein precursor genes and neuronal death in rat hippocampus. Proc Natl Acad Sci USA 90: 9431-9435, 1993 https://doi.org/10.1073/pnas.90.20.9431
  13. Ingaki N, Gonoi T, Clement JP. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science 270: 1166-1170, 1995 https://doi.org/10.1126/science.270.5239.1166
  14. Krieglstein J, Oberpichler-Schwenk H. Primary cultures of neurons for testing neuroprotective drug effects. J Neural Transm Suppl 44: 1-20, 1994 https://doi.org/10.1007/BF01252697
  15. Krnjevic K. Adenosine triphosphate-sensitive potassium channels in anoxia. Stroke 21: Suppl. III-190-III-193, 1990
  16. Lindeman KS, Fernandes LB, Croxton TL, Hirshman CA. Role of potassium channels in hypoxic relaxation of porcine bronchi in vitro. Am J Physiol Mar; 266(3Pt1): L232-237, 1994
  17. Liss B, Roeper J. Molecular physiology of neuronal K-ATP channels. Mol Membr Biol Apr-Jun; 18(2): 117-127, 2001 https://doi.org/10.1080/09687680110047373
  18. Miller R. Glucose-related potassium channels are sweet news for neurobiologists. Trends Neurosci 13: 197-199, 1990 https://doi.org/10.1016/0166-2236(90)90158-7
  19. Noma A. ATP-regulated K$^+$ channels in cardiac muscle. Nature Sep 8-14; 305(5930): 147-148, 1983 https://doi.org/10.1038/305147a0
  20. Ohno-Shosaku T, Yamamoto C. Identification of an ATP-sensitive $^+$ channel in rat cultured cortical neurons. Eur J Physiol 422: 260-266, 1992 https://doi.org/10.1007/BF00376211
  21. Quayle JM, Bonev AD, Brayden JE, Nelson MT. Pharmacology of ATP-sensitive K1 currents in smooth muscle cells. Am J Physiol 269: C1112-C1118, 1995 https://doi.org/10.1152/ajpcell.1995.269.5.C1112
  22. Quayle JM, Nelson MT, Standen NB. ATP-sensitive and inwardly rectifying potassium channels in smooth muscle. A Physiol 77(4): 1165-1232, 1997
  23. Reshef A, Spering O, Zoref-Sani E. Opening of ATP-sensitive potassium channels by cromakalim confers tolerance against chemical ischemia in rat neuronal cultures. Neurosci Lett 2508: 111-114, 1998
  24. Teramoto N, Brading AF. Activation by levcromakalim and metabolic inhibition of glibenclamide-sensitive K channnels in smooth muscle cells of pig proximal urethra. Br J Pharmacol 118: 635-642, 1996 https://doi.org/10.1111/j.1476-5381.1996.tb15448.x