Skip to main content
Log in

Angiotensin II, vasopressin and GTP[γ-S] inhibit inward-rectifying K+ channels in porcine cerebral capillary endothelial cells

  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Summary

Cerebral capillaries from porcine brain were isolated. and endothelial cells were grown in primary culture. The whole-cell tight seal patch-clamp method was applied to freshly isolated single endothelial cells, and cells which were held in culture up to one week. With high K+ solution in the patch pipette and in the bath we observed inward-rectifying K+ currents, showing a time-dependent decay in part of the experiments. Ba2+ (1–10mm) in the bath blocked this current, whereas outside tetraethylammonium (10mm) decreased the peak current but increased the steady-state current. Addition of 1 μm of angiotensin II or of arginine-vasopressin to the extracellular side caused a time-dependent inhibition of the inward-rectifying K+ current in part of the experiments. Addition of 100 μm GTP[γ-S] to the patch pipette blocked the K+ inward rectifier. In cell-attached membrane patches two types of single inward-rectifying K+ channels were observed, with single channel conductances of 7 and 35 pS. Cell-attached patches were also obtained at the antiluminal membrane of intact isolated cerebral capillaries. Only one type of K+ channel withg=30 pS was recorded. In conclusion, inwardly rectifying K+ channels, which can be inhibited by extracellular angiotensin II and arginine-vasopressin, are present in cerebral capillary endothelial cells. The inhibition of this K+ conductance by GTP[γ-S] indicates that G-proteins are involved in channel regulation. It is suggested that angiotensin II and vasopressin regulate K+ transport across the blood-brain barrier, mediating their effects via G-proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Abbott, N.J., Revest, P.A. 1990. Single-channel currents recorded from brain capillary endothelial cells in culture.J. Physiol. 423:105P

    Google Scholar 

  2. Betz, A.L. 1983. Sodium transport from blood to brain: Inhibition by furosemide and amiloride.J. Neurochem. 41:1158–1164

    PubMed  Google Scholar 

  3. Betz, A.L., Firth, J.A., Goldstein, G.W. 1980. Polarity of the blood-brain barrier: Distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells.Brain Res. 192:17–28

    Article  PubMed  Google Scholar 

  4. Betz, A.L., Goldstein, G.W. 1986. Specialized properties and solute transport in brain capillaries.Annu. Rev. Physiol. 48:241–250

    Article  PubMed  Google Scholar 

  5. Biermans, G., Vereecke, J., Carmeliet, E. 1987. The mechanism of the inactivation of the inward-rectifying K current during hyperpolarizing steps in guinea-pig ventricular myocytes.Pfluegers Arch. 410:604–613

    Article  Google Scholar 

  6. Bowman, P.D., Betz, A.L., Ar, D., Wolinsky, J.S., Penney, J.B., Shivers, R.R., Goldstein, G.W. 1981. Primary culture of capillary endothelium from rat brain.In Vitro 17:353–362

    PubMed  Google Scholar 

  7. Bradbury, M.W.B., Stulcová, B. 1970. Efflux mechanism contributing to the stability of the potassium concentration in cerebrospinal fluid.J. Physiol. 280:415–430

    Google Scholar 

  8. Brendel, K., Meezan, E., Carlson, E.C. 1974. Isolated brain microvessels: A purified, metabolically active preparation from bovine cerebral cortex.Science 185:953–955

    PubMed  Google Scholar 

  9. Buijs, R.M. 1987. Vasopressin localization and putative functions in the brain.In: Vasopressin. Principles and Properties. D.M. Gash, and G.J. Boer, editors, pp. 91–115. Plenum, New York-London

    Google Scholar 

  10. Butt, A.M., Jones, H.C., Abbott, N.J. 1990. Electrical resistance across the blood-brain barrier in anaesthetized rats: A developmental study.J. Physiol. 429:47–62

    PubMed  Google Scholar 

  11. Colden-Stanfield, M., Schilling, W.P., Possani, L.D., Kunze, D.L. 1990. Bradykinin-induced potassium current in cultured bovine aortic endothelial cells.J. Membrane Biol. 116:227–238

    Article  Google Scholar 

  12. Crane, J.K., Campanile, C.P., Garrison, J.C. 1982. The hepatic angiotensin II receptor. II. Effect of guanine nucleotides and interaction with cyclic AMP production.J. Biol. Chem. 257:4959–4965

    PubMed  Google Scholar 

  13. Crone, C., Olesen, S.P. 1982. Electrical resistance of brain microvascular endothelium.Brain Res. 241:49–55

    Article  PubMed  Google Scholar 

  14. De Lean, A., Ong, H., Gutkowska, J., Schiller, P.W., McNicoll, N. 1984. Evidence for agonist induced interaction of angiotensin receptor with a guanine nucleotide-binding protein in bovine adrenal zona glomerulosa.Mol. Pharmacol. 26:498–508

    PubMed  Google Scholar 

  15. Edvinsson, L., Hardebo, J.-E., Owman, C. 1979. Effects of angiotensin II on cerebral blood vessels.Acta Physiol. Scand. 105:381–383

    PubMed  Google Scholar 

  16. Eisenberg, H.M., Suddith, R.L. 1979. Cerebral vessels have the capacity to transport sodium and potassium.Science 206:1083–1085

    PubMed  Google Scholar 

  17. Fain, G.L., Farahbakhsh, N.A. 1989. Voltage-activated currents recorded from rabbit pigmented cilliary body epithelial cells in culture.J. Physiol. 418:83–103

    PubMed  Google Scholar 

  18. Fargon, F., McNaughton, P.A., Sepulveda, F.V. 1990. Possible involvement of GTP-binding proteins in the deactivation of an inwardly rectifying K+ current in enterocytes isolated from guinea-pig small intestine.Pfluegers Arch. 417:240–242

    Article  Google Scholar 

  19. Fukushima, Y. 1982. Blocking kinetics of the anomalous potassium rectifier of tunicate egg studied by single channel recording.J. Physiol. 331:311–331

    PubMed  Google Scholar 

  20. Ganten, D., Hermann, K., Bayer, C., Unger, T., Lang, R.E. 1983. Angiotensin synthesis in the brain and increased turnover in hypertensive rats.Science 221:869–871

    PubMed  Google Scholar 

  21. Gögelein, H., Greger, R. 1986. A voltage-dependent ionic channel in the basolateral membrane of late proximal tubule of the rabbit kidney.Pfluegers Arch. 407:S142-S148

    Article  Google Scholar 

  22. Goldstein, G.W. 1979. Relation of potassium transport to oxidative metabolism in isolated brain capillaries.J. Physiol. 286:185–195

    PubMed  Google Scholar 

  23. Goldstein, G.W., Betz, A.L., Bowman, P.D. 1984. Use of isolated brain capillaries and cultured endothelial cells to study the blood-brain barrier.Fed. Proc. 43:191–195

    PubMed  Google Scholar 

  24. Goldstein, G.W., Wolinsky, J.S., Csejtey, J., Diamond, J. 1975. Isolation of metabolically active capillaries from rat brain.J. Neurochem. 25:715–717

    PubMed  Google Scholar 

  25. Grammas, P., Diglio, C., Giacomelli, F., Wiener, J. 1989. Cerebrovascular angitonesin II receptors in spontaneously hypertensive rats.J. Cardiovasc. Pharmacol. 13:227–232

    PubMed  Google Scholar 

  26. Grubb, R.L., Raichle, M.E. 1981. Intraventricular angiotensin II increases brain vascular permeability.Brain Res. 210:426–430

    Article  PubMed  Google Scholar 

  27. Haberl, R.L., Anneser, F., Villringer, A., Einhäupl, K.M. 1990. Angiotensin II induces endothelium-dependent vasodilation of rat cerebral arterioles.Am. J. Physiol. 258:H1840-H1846

    PubMed  Google Scholar 

  28. Hamill, O.P., Marty, A., Neher, E., Sakmann, B., Sigworth, F.J. 1981. Improved patch-clamp techniques for high-resolution current recordings from cells and cell-free membrane patches.Pfluegers Arch. 391:85–100

    Article  Google Scholar 

  29. Hansen, A.J., Lund-Andersen, H., Crone, C. 1977. K+-permeability of the blood-brain barrier, investigated by aid of a K+-sensitive microelectrode.Acta Physiol. Scand. 101:438–445

    PubMed  Google Scholar 

  30. Herbst, T.J., Raichle, M.E., Ferrendelli, J.A. 1979. β-adrenergic regulation of adenosine 3′,5′-monophosphate concentration in brain microvessels.Science 204:330–332

    PubMed  Google Scholar 

  31. Johns, A., Lategan, T.W., Lodge, N.J., Ryan, U.S., Van Breemen, C., Adams, D.J. 1987. Calcium entry through receptor-operated channels in bovine pulmonary artery endothelial cells.Tissue Cell 19:733–745

    Article  PubMed  Google Scholar 

  32. Josephson, I.R., Brown, A.M. 1986. Inward-rectifying single-channel and whole cell K+ currents in rat ventricular myocytes.J. Membrane Biol. 94:19–35

    Article  Google Scholar 

  33. Katusic, Z.S., Sheperd, J.T., Vanhoutte, P.M. 1984. Vasopressin causes endothelium-dependent relaxations of the canine basilar artery.Circ. Res. 55:575–579

    PubMed  Google Scholar 

  34. Katz, B. 1949. Les constantes electriques de la membranes du muscle.Arch. Sci. Physiol. 3:285–300

    Google Scholar 

  35. Katzman, R. 1976. Maintenance of a constant brain extracellular potassium.Fed. Proc. 35:1244–1247

    PubMed  Google Scholar 

  36. Kobayashi, H., Magnoni, M.S., Govoni, S., Izumi, F., Wada, A., Trabucchi, M. 1985. Neuronal control of brain microvessel function.Experientia 41:427–558

    Article  PubMed  Google Scholar 

  37. Kretzschmar, R., Landgraf, R., Gjedde, A., Ermisch, A. 1986. Vasopressin binds to microvessels from rat hippocampus.Brain Res. 380:325–330

    Article  PubMed  Google Scholar 

  38. Kurtz, A., Penner, R. 1989. Angiotensin II induces oscillations of intracellular calcium and blocks anomalous inwardrectifying potassium current in mouse renal juxtaglomerular cells.Proc. Natl. Acad. Sci. USA 86:3423–3427

    PubMed  Google Scholar 

  39. Lindau, M., Fernandez, J.M. 1986. A patch-clamp study of histamin-secreting cells.J. Gen. Physiol. 88:349–368

    Article  PubMed  Google Scholar 

  40. Martin, S.C., Yule, D.I., Dunne, M.J., Gallacher, D.V., Petersen, O.H. 1989. Vasopressin directly closes ATP-sensitive potassium channels evoking membrane depolarization and an increase in the free intracellular Ca2+ concentration in insulin-secreting cells.EMBO J. 8:3595–3599

    PubMed  Google Scholar 

  41. McCloskey, M.A., Cahalan, M.D. 1990. G protein control of potassium channel activity in a mast cell line.J. Gen. Physiol. 95:205–227

    Article  PubMed  Google Scholar 

  42. Meyer, J., Mischek, U., Veyhl, M., Henzel, K., Galla, H.-J. 1990. Blood-brain barrier characteristic enzymatic properties in cultured brain capillary endothelial cells.Brain Res. 514:305–309

    Article  PubMed  Google Scholar 

  43. Mischek, U., Meyer, J., Galla H.-J. 1989. Characterization of Γ-glutamyl transpeptidase activity of cultured endothelial cells from porcine brain capillaries.Cell Tissue Res. 256:221–226

    PubMed  Google Scholar 

  44. Nakajima, Y., Nakajima, S., Inoue, M. 1988. Pertussis toxininsensitive G protein mediates substance P-induced inhibition of potassium channels in brain neurons.Proc. Natl. Acad. Sci. USA 85:3643–3647

    PubMed  Google Scholar 

  45. Ohmori, H., Yoshida, S., Hagiwara, S. 1981. Single K+ channel currents of anomalous rectification in cultured rat myotubes.Proc. Natl. Acad. Sci. USA 78:4960–4964

    PubMed  Google Scholar 

  46. Orlowski, M., Sessa, G., Green, J.P. 1974. Γ-glutamyl transpeptidase in brain capillaries: Possible site of a blood-brain barrier for amino acids.Science 184:66–68

    PubMed  Google Scholar 

  47. Pobiner, B.F., Hewlett, E.L., Garrison, J.C. 1985. Role of N i in coupling angiotensin receptors to inhibition of adenylate cyclase in hepatocytes.J. Biol. Chem. 260:16200–16209

    PubMed  Google Scholar 

  48. Raichle, M.E., Grubb, R.L. 1978. Regulation of brain water permeability by centrally-released vasopressin.Brain Res. 143:191–194

    Article  PubMed  Google Scholar 

  49. Sakmann, B., Trube, G. 1984. Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart.J. Physiol. 347:641–657

    PubMed  Google Scholar 

  50. Sakmann, B., Trube, G. 1984. Voltage-dependent inactivation of inward-rectifying single-channel currents in the guinea-pig heart cell membrane.J. Physiol. 347:659–683

    PubMed  Google Scholar 

  51. Sauve, R., Roy, G., Payet, D. 1983. Single channel K+ currents from HeLa cells.J. Membrane Biol. 74:41–49

    Article  Google Scholar 

  52. Silver, M.R., De Coursey, T.E. 1990. Intrinsic gating of inward rectifier in bovine pulmonary artery endothelial cells in the presence or absence of internal Mg2+.J. Gen. Physiol. 96:109–133

    Article  PubMed  Google Scholar 

  53. Speth, R.C., Harik, S.I. 1985. Angiotensin II receptor binding sites in brain microvessels.Proc. Natl. Acad. Sci. USA 82:6340–6343

    PubMed  Google Scholar 

  54. Toro, L., Amador, M., Stefani, E. 1990. ANG II inhibits calcium-activated potassium channels from coronary smooth muscle in lipid bilayers.Am. J. Physiol. 258:H912-H915

    PubMed  Google Scholar 

  55. Uhing, R.J., Prpic, V., Jiang, H., Exton, J.H. 1986. Hormone-stimulated polyphosphoinositide breakdown in rat liver plasma membranes.J. Biol. Chem. 261:2140–2146

    PubMed  Google Scholar 

  56. Vigne, P., Champigny, G., Marsault, R., Barbry, P., Frelin, C., Lazdunski, M. 1989. A new type of amiloride-sensitive cationic channel in endothelial cells of brain microvessels.J. Biol. Chem. 264:7663–7668

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hoyer, J., Popp, R., Meyer, J. et al. Angiotensin II, vasopressin and GTP[γ-S] inhibit inward-rectifying K+ channels in porcine cerebral capillary endothelial cells. J. Membrain Biol. 123, 55–62 (1991). https://doi.org/10.1007/BF01993963

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01993963

Key Words

Navigation