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. 1996 Jul 15;494(Pt 2):399–409. doi: 10.1113/jphysiol.1996.sp021501

ATP-sensitive K+ channels are functional in expiratory neurones of normoxic cats.

O Pierrefiche 1, A M Bischoff 1, D W Richter 1
PMCID: PMC1160643  PMID: 8842000

Abstract

1. We analysed spontaneously active expiratory neurones (n = 48) of anaesthetized cats for the presence of ATP-sensitive K+ (KATP) channels. 2. Intracellular injection of ATP reversibly depolarized neurones during all phases of the respiratory cycle. During expiration, membrane potential depolarized by an average of 1.5 +/- 0.1 mV leading to a 25% increase of discharge frequency. During inspiration, ATP induced a 1.8 +/- 0.2 mV depolarization, which was accompanied by a maximum of 20% increase of input resistance (Rn). 3. Extracellular application of diazoxide, an agonist of KATP channels, resulted in reversible membrane hyperpolarization in 68% of neurones (n = 19). This hyperpolarization (2.5 mV during expiration and 3.1 mV during inspiration) was accompanied by a 22% decrease in Rn. 4. Extracellular application of tolbutamide and glibenclamide, two antagonists of KATP channels, evoked reversible depolarizations in 76% of neurones (n = 21). The depolarization was relatively constant throughout the respiratory cycle (1.4 mV during expiration and 2.3 mV during inspiration). Rn increased by 22%. 5. The same sulphonylureas also changed the steepness of membrane depolarization when neurones escaped spontaneous synaptic inhibition during postinspiration. Extracellularly applied tolbutamide and glibenclamide increased the steepness of depolarization by 21%, while diazoxide reduced it by 20%. 6. Antagonism of drugs was verified by simultaneous extra- and intracellular application of diazoxide and glibenclamide, respectively. 7. During voltage clamp at holding potential at -60 to -67 mV, intracellular or extracellular application of tolbutamide and glibenclamide blocked a persistent outward current. 8. We conclude that KATP channels are functional in expiratory neurones of adult cats and contribute to the control of excitability even during normoxia.

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Selected References

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  1. Aguilar-Bryan L., Nichols C. G., Wechsler S. W., Clement J. P., 4th, Boyd A. E., 3rd, González G., Herrera-Sosa H., Nguy K., Bryan J., Nelson D. A. Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science. 1995 Apr 21;268(5209):423–426. doi: 10.1126/science.7716547. [DOI] [PubMed] [Google Scholar]
  2. Ashcroft F. M. Adenosine 5'-triphosphate-sensitive potassium channels. Annu Rev Neurosci. 1988;11:97–118. doi: 10.1146/annurev.ne.11.030188.000525. [DOI] [PubMed] [Google Scholar]
  3. Ashcroft S. J., Ashcroft F. M. Properties and functions of ATP-sensitive K-channels. Cell Signal. 1990;2(3):197–214. doi: 10.1016/0898-6568(90)90048-f. [DOI] [PubMed] [Google Scholar]
  4. Ashford M. L., Boden P. R., Treherne J. M. Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K+ channels. Pflugers Arch. 1990 Jan;415(4):479–483. doi: 10.1007/BF00373626. [DOI] [PubMed] [Google Scholar]
  5. Ashford M. L., Bond C. T., Blair T. A., Adelman J. P. Cloning and functional expression of a rat heart KATP channel. Nature. 1994 Aug 11;370(6489):456–459. doi: 10.1038/370456a0. [DOI] [PubMed] [Google Scholar]
  6. Ashford M. L., Sturgess N. C., Trout N. J., Gardner N. J., Hales C. N. Adenosine-5'-triphosphate-sensitive ion channels in neonatal rat cultured central neurones. Pflugers Arch. 1988 Aug;412(3):297–304. doi: 10.1007/BF00582512. [DOI] [PubMed] [Google Scholar]
  7. Ballanyi K., Mückenhoff K., Bellingham M. C., Okada Y., Scheid P., Richter D. W. Activity-related pH changes in respiratory neurones and glial cells of cats. Neuroreport. 1994 Dec 30;6(1):33–36. doi: 10.1097/00001756-199412300-00010. [DOI] [PubMed] [Google Scholar]
  8. Ballanyi K., Völker A., Richter D. W. Anoxia induced functional inactivation of neonatal respiratory neurones in vitro. Neuroreport. 1994 Dec 30;6(1):165–168. doi: 10.1097/00001756-199412300-00042. [DOI] [PubMed] [Google Scholar]
  9. Brockhaus J., Ballanyi K., Smith J. C., Richter D. W. Microenvironment of respiratory neurons in the in vitro brainstem-spinal cord of neonatal rats. J Physiol. 1993 Mar;462:421–445. doi: 10.1113/jphysiol.1993.sp019562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Champagnat J., Richter D. W. The roles of K+ conductance in expiratory pattern generation in anaesthetized cats. J Physiol. 1994 Aug 15;479(Pt 1):127–138. doi: 10.1113/jphysiol.1994.sp020282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Crépel V., Krnjević K., Ben-Ari Y. Sulphonylureas reduce the slowly inactivating D-type outward current in rat hippocampal neurons. J Physiol. 1993 Jul;466:39–54. [PMC free article] [PubMed] [Google Scholar]
  12. Dunne M. J., Petersen O. H. Intracellular ADP activates K+ channels that are inhibited by ATP in an insulin-secreting cell line. FEBS Lett. 1986 Nov 10;208(1):59–62. doi: 10.1016/0014-5793(86)81532-0. [DOI] [PubMed] [Google Scholar]
  13. Findlay I. Effects of pH upon the inhibition by sulphonylurea drugs of ATP-sensitive K+ channels in cardiac muscle. J Pharmacol Exp Ther. 1992 Jul;262(1):71–79. [PubMed] [Google Scholar]
  14. Finta E. P., Harms L., Sevcik J., Fischer H. D., Illes P. Effects of potassium channel openers and their antagonists on rat locus coeruleus neurones. Br J Pharmacol. 1993 Jun;109(2):308–315. doi: 10.1111/j.1476-5381.1993.tb13571.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Haji A., Remmers J. E., Connelly C., Takeda R. Effects of glycine and GABA on bulbar respiratory neurons of cat. J Neurophysiol. 1990 May;63(5):955–965. doi: 10.1152/jn.1990.63.5.955. [DOI] [PubMed] [Google Scholar]
  16. Jiang C., Xia Y., Haddad G. G. Role of ATP-sensitive K+ channels during anoxia: major differences between rat (newborn and adult) and turtle neurons. J Physiol. 1992 Mar;448:599–612. doi: 10.1113/jphysiol.1992.sp019060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jonas P., Koh D. S., Kampe K., Hermsteiner M., Vogel W. ATP-sensitive and Ca-activated K channels in vertebrate axons: novel links between metabolism and excitability. Pflugers Arch. 1991 Mar;418(1-2):68–73. doi: 10.1007/BF00370453. [DOI] [PubMed] [Google Scholar]
  18. Mifflin S., Richter D. W. The effects of QX-314 on medullary respiratory neurones. Brain Res. 1987 Sep 8;420(1):22–31. doi: 10.1016/0006-8993(87)90235-6. [DOI] [PubMed] [Google Scholar]
  19. Mourre C., Ben Ari Y., Bernardi H., Fosset M., Lazdunski M. Antidiabetic sulfonylureas: localization of binding sites in the brain and effects on the hyperpolarization induced by anoxia in hippocampal slices. Brain Res. 1989 May 1;486(1):159–164. doi: 10.1016/0006-8993(89)91288-2. [DOI] [PubMed] [Google Scholar]
  20. Mourre C., Widmann C., Lazdunski M. Sulfonylurea binding sites associated with ATP-regulated K+ channels in the central nervous system: autoradiographic analysis of their distribution and ontogenesis, and of their localization in mutant mice cerebellum. Brain Res. 1990 Jun 11;519(1-2):29–43. doi: 10.1016/0006-8993(90)90057-i. [DOI] [PubMed] [Google Scholar]
  21. Panten U., Heipel C., Rosenberger F., Scheffer K., Zünkler B. J., Schwanstecher C. Tolbutamide-sensitivity of the adenosine 5'-triphosphate-dependent K+ channel in mouse pancreatic B-cells. Naunyn Schmiedebergs Arch Pharmacol. 1990 Nov;342(5):566–574. doi: 10.1007/BF00169047. [DOI] [PubMed] [Google Scholar]
  22. Philipson L. H., Steiner D. F. Pas de deux or more: the sulfonylurea receptor and K+ channels. Science. 1995 Apr 21;268(5209):372–373. doi: 10.1126/science.7716539. [DOI] [PubMed] [Google Scholar]
  23. Pierrefiche O., Champagnat J., Richter D. W. Calcium-dependent conductances control neurones involved in termination of inspiration in cats. Neurosci Lett. 1995 Jan 23;184(2):101–104. doi: 10.1016/0304-3940(94)11179-m. [DOI] [PubMed] [Google Scholar]
  24. Richter D. W., Bischoff A., Anders K., Bellingham M., Windhorst U. Response of the medullary respiratory network of the cat to hypoxia. J Physiol. 1991 Nov;443:231–256. doi: 10.1113/jphysiol.1991.sp018832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Richter D. W., Camerer H., Sonnhof U. Changes in extracellular potassium during the spontaneous activity of medullary respiratory neurones. Pflugers Arch. 1978 Sep 6;376(2):139–149. doi: 10.1007/BF00581577. [DOI] [PubMed] [Google Scholar]
  26. Richter D. W., Champagnat J., Jacquin T., Benacka R. Calcium currents and calcium-dependent potassium currents in mammalian medullary respiratory neurones. J Physiol. 1993 Oct;470:23–33. doi: 10.1113/jphysiol.1993.sp019844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Richter D. W. Generation and maintenance of the respiratory rhythm. J Exp Biol. 1982 Oct;100:93–107. doi: 10.1242/jeb.100.1.93. [DOI] [PubMed] [Google Scholar]
  28. Roeper J., Hainsworth A. H., Ashcroft F. M. Tolbutamide reverses membrane hyperpolarisation induced by activation of D2 receptors and GABAB receptors in isolated substantia nigra neurones. Pflugers Arch. 1990 Jun;416(4):473–475. doi: 10.1007/BF00370758. [DOI] [PubMed] [Google Scholar]
  29. Schmidt C., Bellingham M. C., Richter D. W. Adenosinergic modulation of respiratory neurones and hypoxic responses in the anaesthetized cat. J Physiol. 1995 Mar 15;483(Pt 3):769–781. doi: 10.1113/jphysiol.1995.sp020621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schwanstecher C., Panten U. Identification of an ATP-sensitive K+ channel in spiny neurons of rat caudate nucleus. Pflugers Arch. 1994 May;427(1-2):187–189. doi: 10.1007/BF00585961. [DOI] [PubMed] [Google Scholar]
  31. Schwanstecher M., Schwanstecher C., Dickel C., Chudziak F., Moshiri A., Panten U. Location of the sulphonylurea receptor at the cytoplasmic face of the beta-cell membrane. Br J Pharmacol. 1994 Nov;113(3):903–911. doi: 10.1111/j.1476-5381.1994.tb17078.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Trapp S., Ballanyi K., Richter D. W. Spontaneous activation of KATP current in rat dorsal vagal neurones. Neuroreport. 1994 Jun 2;5(10):1285–1288. doi: 10.1097/00001756-199406020-00033. [DOI] [PubMed] [Google Scholar]
  33. Trippenbach T., Richter D. W., Acker H. Hypoxia and ion activities within the brain stem of newborn rabbits. J Appl Physiol (1985) 1990 Jun;68(6):2494–2503. doi: 10.1152/jappl.1990.68.6.2494. [DOI] [PubMed] [Google Scholar]
  34. Trube G., Rorsman P., Ohno-Shosaku T. Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+ channel in mouse pancreatic beta-cells. Pflugers Arch. 1986 Nov;407(5):493–499. doi: 10.1007/BF00657506. [DOI] [PubMed] [Google Scholar]
  35. Zini S., Roisin M. P., Langel U., Bartfai T., Ben-Ari Y. Galanin reduces release of endogenous excitatory amino acids in the rat hippocampus. Eur J Pharmacol. 1993 Mar 15;245(1):1–7. doi: 10.1016/0922-4106(93)90162-3. [DOI] [PubMed] [Google Scholar]
  36. Zünkler B. J., Lins S., Ohno-Shosaku T., Trube G., Panten U. Cytosolic ADP enhances the sensitivity to tolbutamide of ATP-dependent K+ channels from pancreatic B-cells. FEBS Lett. 1988 Nov 7;239(2):241–244. doi: 10.1016/0014-5793(88)80925-6. [DOI] [PubMed] [Google Scholar]

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