Skip to main content
PMC home page
The Journal of General Physiology logoLink to The Journal of General Physiology
. 1989 Mar 1;93(3):451–472. doi: 10.1085/jgp.93.3.451

Voltage-gated potassium channels in brown fat cells

PMCID: PMC2216218  PMID: 2467964

Abstract

We studied the membrane currents of isolated cultured brown fat cells from neonatal rats using whole-cell and single-channel voltage-clamp recording. All brown fat cells that were recorded from had voltage- gated K currents as their predominant membrane current. No inward currents were seen in these experiments. The K currents of brown fat cells resemble the delayed rectifier currents of nerve and muscle cells. The channels were highly selective for K+, showing a 58-mV change in reversal potential for a 10-fold change in the external [K+]. Their selectivity was typical for K channels, with relative permeabilities of K+ greater than Rb+ greater than NH+4 much greater than Cs+, Na+. The K currents in brown adipocytes activated with a sigmoidal delay after depolarizations to membrane potentials positive to -50 mV. Activation was half maximal at a potential of -28 mV and did not require the presence of significant concentrations of internal calcium. Maximal voltage-activated K conductance averaged 20 nS in high external K+ solutions. The K currents inactivated slowly with sustained depolarization with time constants for the inactivation process on the order of hundreds of milliseconds to tens of seconds. The K channels had an average single-channel conductance of 9 pS and a channel density of approximately 1,000 channels/cell. The K current was blocked by tetraethylammonium or 4-aminopyridine with half maximal block occurring at concentrations of 1-2 mM for either blocker. K currents were unaffected by two blockers of Ca2+-activated K channels, charybdotoxin and apamin. Bath-applied norepinephrine did not affect the K currents or other membrane currents under our experimental conditions. These properties of the K channels indicate that they could produce an increase in the K+ permeability of the brown fat cell membrane during the depolarization that accompanies norepinephrine-stimulated thermogenesis, but that they do not contribute directly to the norepinephrine-induced depolarization.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armstrong C. M., Bezanilla F. Charge movement associated with the opening and closing of the activation gates of the Na channels. J Gen Physiol. 1974 May;63(5):533–552. doi: 10.1085/jgp.63.5.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blatz A. L., Magleby K. L. Single apamin-blocked Ca-activated K+ channels of small conductance in cultured rat skeletal muscle. Nature. 1986 Oct 23;323(6090):718–720. doi: 10.1038/323718a0. [DOI] [PubMed] [Google Scholar]
  3. Cahalan M. D., Chandy K. G., DeCoursey T. E., Gupta S. A voltage-gated potassium channel in human T lymphocytes. J Physiol. 1985 Jan;358:197–237. doi: 10.1113/jphysiol.1985.sp015548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Connolly E., Nånberg E., Nedergaard J. Na+-dependent, alpha-adrenergic mobilization of intracellular (mitochondrial) Ca2+ in brown adipocytes. Eur J Biochem. 1984 May 15;141(1):187–193. doi: 10.1111/j.1432-1033.1984.tb08173.x. [DOI] [PubMed] [Google Scholar]
  5. Connolly E., Nånberg E., Nedergaard J. Norepinephrine-induced Na+ influx in brown adipocytes is cyclic AMP-mediated. J Biol Chem. 1986 Nov 5;261(31):14377–14385. [PubMed] [Google Scholar]
  6. DeCoursey T. E., Chandy K. G., Gupta S., Cahalan M. D. Voltage-gated K+ channels in human T lymphocytes: a role in mitogenesis? Nature. 1984 Feb 2;307(5950):465–468. doi: 10.1038/307465a0. [DOI] [PubMed] [Google Scholar]
  7. Fain J. N., Reed N., Saperstein R. The isolation and metabolism of brown fat cells. J Biol Chem. 1967 Apr 25;242(8):1887–1894. [PubMed] [Google Scholar]
  8. Fink S. A., Williams J. A. Adrenergic receptors mediating depolarization in brown adipose tissue. Am J Physiol. 1976 Sep;231(3):700–706. doi: 10.1152/ajplegacy.1976.231.3.700. [DOI] [PubMed] [Google Scholar]
  9. Foster D. O., Frydman M. L. Nonshivering thermogenesis in the rat. II. Measurements of blood flow with microspheres point to brown adipose tissue as the dominant site of the calorigenesis induced by noradrenaline. Can J Physiol Pharmacol. 1978 Feb;56(1):110–122. doi: 10.1139/y78-015. [DOI] [PubMed] [Google Scholar]
  10. Giovannini P., Seydoux J., Girardier L. Evidence for a modulating effect of Na+/H+ exchange on the metabolic response of rat brown adipose tissue. Pflugers Arch. 1988 Mar;411(3):273–277. doi: 10.1007/BF00585114. [DOI] [PubMed] [Google Scholar]
  11. Girardier L., Schneider-Picard G. Alpha and beta-adrenergic mediation of membrane potential changes and metabolism in rat brown adipose tissue. J Physiol. 1983 Feb;335:629–641. doi: 10.1113/jphysiol.1983.sp014555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Girardier L., Seydoux J., Clausen T. Membrane potential of brown adipose tissue. A suggested mechanism for the regulation of thermogenesis. J Gen Physiol. 1968 Dec;52(6):925–940. doi: 10.1085/jgp.52.6.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HODGKIN A. L., KATZ B. The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol. 1949 Mar 1;108(1):37–77. doi: 10.1113/jphysiol.1949.sp004310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  15. Herd P. A., Hammond R. P., Hamolsky M. W. Sodium pump activity during norepinephrine-stimulated respiration in brown adipocytes. Am J Physiol. 1973 Jun;224(6):1300–1304. doi: 10.1152/ajplegacy.1973.224.6.1300. [DOI] [PubMed] [Google Scholar]
  16. Horowitz J. M., Horwitz B. A., Smith R. E. Effect in vivo of norepinephrine on the membrane resistance of brown fat cells. Experientia. 1971 Dec 15;27(12):1419–1421. doi: 10.1007/BF02154265. [DOI] [PubMed] [Google Scholar]
  17. Horwitz B. A., Hamilton J. Alpha-adrenergic-induced changes in hamster (Mesocricetus) brown adipocyte respiration and membrane potential. Comp Biochem Physiol C. 1984;78(1):99–104. doi: 10.1016/0742-8413(84)90053-7. [DOI] [PubMed] [Google Scholar]
  18. Horwitz B. A. Ouabain-sensitive component of brown fat thermogenesis. Am J Physiol. 1973 Feb;224(2):352–355. doi: 10.1152/ajplegacy.1973.224.2.352. [DOI] [PubMed] [Google Scholar]
  19. Kuusela P., Nedergaard J., Cannon B. Beta-adrenergic stimulation of fatty acid release from brown fat cells differentiated in monolayer culture. Life Sci. 1986 Feb 17;38(7):589–599. doi: 10.1016/0024-3205(86)90052-4. [DOI] [PubMed] [Google Scholar]
  20. LaNoue K. F., Koch C., Strzelecka D., Kobylski T. P. Regulation of Na+ transport in brown adipose tissue. Biochem J. 1986 Apr 15;235(2):545–552. doi: 10.1042/bj2350545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lee S. C., Sabath D. E., Deutsch C., Prystowsky M. B. Increased voltage-gated potassium conductance during interleukin 2-stimulated proliferation of a mouse helper T lymphocyte clone. J Cell Biol. 1986 Apr;102(4):1200–1208. doi: 10.1083/jcb.102.4.1200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Marchais D., Marty A. Interaction of permeant ions with channels activated by acetylcholine in Aplysia neurones. J Physiol. 1979 Dec;297(0):9–45. doi: 10.1113/jphysiol.1979.sp013025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Marchetti C., Premont R. T., Brown A. M. A whole-cell and single-channel study of the voltage-dependent outward potassium current in avian hepatocytes. J Gen Physiol. 1988 Feb;91(2):255–274. doi: 10.1085/jgp.91.2.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Matteson D. R., Swenson R. P., Jr External monovalent cations that impede the closing of K channels. J Gen Physiol. 1986 May;87(5):795–816. doi: 10.1085/jgp.87.5.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Meech R. W., Standen N. B. Potassium activation in Helix aspersa neurones under voltage clamp: a component mediated by calcium influx. J Physiol. 1975 Jul;249(2):211–239. doi: 10.1113/jphysiol.1975.sp011012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miller C., Moczydlowski E., Latorre R., Phillips M. Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle. Nature. 1985 Jan 24;313(6000):316–318. doi: 10.1038/313316a0. [DOI] [PubMed] [Google Scholar]
  27. Nedergaard J. Effects of cations on brown adipose tissue in relation to possible metabolic consequences of membrane depolarisation. Eur J Biochem. 1981;114(1):159–167. doi: 10.1111/j.1432-1033.1981.tb06187.x. [DOI] [PubMed] [Google Scholar]
  28. Nedergaard J., Lindberg O. The brown fat cell. Int Rev Cytol. 1982;74:187–286. doi: 10.1016/s0074-7696(08)61173-0. [DOI] [PubMed] [Google Scholar]
  29. Nicholls D. G., Locke R. M. Thermogenic mechanisms in brown fat. Physiol Rev. 1984 Jan;64(1):1–64. doi: 10.1152/physrev.1984.64.1.1. [DOI] [PubMed] [Google Scholar]
  30. Nånberg E., Connolly E., Nedergaard J. Presence of a Ca2+-dependent K+ channel in brown adipocytes. Possible role in maintenance of alpha 1-adrenergic stimulation. Biochim Biophys Acta. 1985 Jan 18;844(1):42–49. doi: 10.1016/0167-4889(85)90231-9. [DOI] [PubMed] [Google Scholar]
  31. Nånberg E., Nedergaard J., Cannon B. Alpha-adrenergic effects on 86Rb+ (K+) potentials and fluxes in brown fat cells. Biochim Biophys Acta. 1984 Jul 20;804(3):291–300. doi: 10.1016/0167-4889(84)90132-0. [DOI] [PubMed] [Google Scholar]
  32. Pappone P. A., Cahalan M. D. Pandinus imperator scorpion venom blocks voltage-gated potassium channels in nerve fibers. J Neurosci. 1987 Oct;7(10):3300–3305. doi: 10.1523/JNEUROSCI.07-10-03300.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pappone P. A., Lucero M. T. Pandinus imperator scorpion venom blocks voltage-gated potassium channels in GH3 cells. J Gen Physiol. 1988 Jun;91(6):817–833. doi: 10.1085/jgp.91.6.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rothwell N. J., Stock M. J. A role for brown adipose tissue in diet-induced thermogenesis. Nature. 1979 Sep 6;281(5726):31–35. doi: 10.1038/281031a0. [DOI] [PubMed] [Google Scholar]
  35. Schneider-Picard G., Coles J. A., Girardier L. Alpha- and beta-adrenergic mediation of changes in metabolism and Na/K exchange in rat brown fat. J Gen Physiol. 1985 Aug;86(2):169–188. doi: 10.1085/jgp.86.2.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Siemen D., Reuhl T. Non-selective cationic channel in primary cultured cells of brown adipose tissue. Pflugers Arch. 1987 May;408(5):534–536. doi: 10.1007/BF00585082. [DOI] [PubMed] [Google Scholar]
  37. Skala J. P. Mechanisms of hormonal regulations in brown adipose tissue of developing rats. Can J Biochem Cell Biol. 1984 Jul;62(7):637–647. doi: 10.1139/o84-085. [DOI] [PubMed] [Google Scholar]
  38. Smith R. E., Horwitz B. A. Brown fat and thermogenesis. Physiol Rev. 1969 Apr;49(2):330–425. doi: 10.1152/physrev.1969.49.2.330. [DOI] [PubMed] [Google Scholar]
  39. Swenson R. P., Jr, Armstrong C. M. K+ channels close more slowly in the presence of external K+ and Rb+. Nature. 1981 Jun 4;291(5814):427–429. doi: 10.1038/291427a0. [DOI] [PubMed] [Google Scholar]
  40. Thompson S. Aminopyridine block of transient potassium current. J Gen Physiol. 1982 Jul;80(1):1–18. doi: 10.1085/jgp.80.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wickler S. J., Horwitz B. A., Flaim S. F., LaNoue K. F. Isoproterenol-induced blood flow in rats acclimated to room temperature and cold. Am J Physiol. 1984 May;246(5 Pt 2):R747–R752. doi: 10.1152/ajpregu.1984.246.5.R747. [DOI] [PubMed] [Google Scholar]
  42. Williams J. A., Matthews E. K. Effects of ions and metabolic inhibitors on membrane potential of brown adipose tissue. Am J Physiol. 1974 Oct;227(4):981–986. doi: 10.1152/ajplegacy.1974.227.4.981. [DOI] [PubMed] [Google Scholar]
  43. Williams J. A., Matthews E. K. Membrane depolarization, cyclic AMP, and glycerol release by brown adipose tissue. Am J Physiol. 1974 Oct;227(4):987–992. doi: 10.1152/ajplegacy.1974.227.4.987. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of General Physiology are provided here courtesy of The Rockefeller University Press

RESOURCES