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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Mar 15;91(6):2367–2371. doi: 10.1073/pnas.91.6.2367

Ca2+ influx through stretch-activated cation channels activates maxi K+ channels in porcine endocardial endothelium.

J Hoyer 1, A Distler 1, W Haase 1, H Gögelein 1
PMCID: PMC43372  PMID: 7510889

Abstract

The endocardial endothelium is an important modulator of myocardial function. The present study demonstrates the existence of a stretch-activated Ca(2+)-permeable cation channel and of a Ca(2+)-activated K+ channel in the endocardial endothelium of the porcine right atrium. The stretch-activated channel is permeable for K+, Na+, Ca2+, and Ba2+, with mean conductances of approximately 32 pS for the monovalent cations and approximately 13 pS for divalent cations. The Ca(2+)-activated K+ channel has a mean conductance of 192 pS in symmetrical KCl. solution. Channel activity is strongly dependent on membrane potential and the cytosolic Ca2+ concentration. Half-maximal activation occurs at a cytosolic Ca2+ concentration of approximately 5 microM. The influx of Ca2+ through the stretch-activated channel is sufficient to activate the Ca(2+)-activated K+ channel in cell-attached patches. Upon activation of the stretch-activated channel, the cytosolic Ca2+ concentration increases, at least locally, to values of approximately 0.5 microM, as deduced from the open probability of the Ca(2+)-dependent K+ channel that was activated simultaneously. The stretch-activated channels are capable of inducing an intracellular Ca2+ signal and may have a role as mechanosensors in the atrial endothelium, possibly activated by atrial overload.

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Selected References

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  1. Adams D. J., Barakeh J., Laskey R., Van Breemen C. Ion channels and regulation of intracellular calcium in vascular endothelial cells. FASEB J. 1989 Oct;3(12):2389–2400. doi: 10.1096/fasebj.3.12.2477294. [DOI] [PubMed] [Google Scholar]
  2. Bregestovski P., Bakhramov A., Danilov S., Moldobaeva A., Takeda K. Histamine-induced inward currents in cultured endothelial cells from human umbilical vein. Br J Pharmacol. 1988 Oct;95(2):429–436. doi: 10.1111/j.1476-5381.1988.tb11663.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brutsaert D. L., Andries L. J. The endocardial endothelium. Am J Physiol. 1992 Oct;263(4 Pt 2):H985–1002. doi: 10.1152/ajpheart.1992.263.4.H985. [DOI] [PubMed] [Google Scholar]
  4. Brutsaert D. L., Meulemans A. L., Sipido K. R., Sys S. U. Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle. Circ Res. 1988 Feb;62(2):358–366. doi: 10.1161/01.res.62.2.358. [DOI] [PubMed] [Google Scholar]
  5. Bustamante J. O., Ruknudin A., Sachs F. Stretch-activated channels in heart cells: relevance to cardiac hypertrophy. J Cardiovasc Pharmacol. 1991;17 (Suppl 2):S110–S113. doi: 10.1097/00005344-199117002-00024. [DOI] [PubMed] [Google Scholar]
  6. Christensen O. Mediation of cell volume regulation by Ca2+ influx through stretch-activated channels. Nature. 1987 Nov 5;330(6143):66–68. doi: 10.1038/330066a0. [DOI] [PubMed] [Google Scholar]
  7. Christensen O., Zeuthen T. Maxi K+ channels in leaky epithelia are regulated by intracellular Ca2+, pH and membrane potential. Pflugers Arch. 1987 Mar;408(3):249–259. doi: 10.1007/BF02181467. [DOI] [PubMed] [Google Scholar]
  8. Colden-Stanfield M., Cramer E. B., Gallin E. K. Comparison of apical and basal surfaces of confluent endothelial cells: patch-clamp and viral studies. Am J Physiol. 1992 Sep;263(3 Pt 1):C573–C583. doi: 10.1152/ajpcell.1992.263.3.C573. [DOI] [PubMed] [Google Scholar]
  9. Davis M. J., Donovitz J. A., Hood J. D. Stretch-activated single-channel and whole cell currents in vascular smooth muscle cells. Am J Physiol. 1992 Apr;262(4 Pt 1):C1083–C1088. doi: 10.1152/ajpcell.1992.262.4.C1083. [DOI] [PubMed] [Google Scholar]
  10. Fichtner H., Fröbe U., Busse R., Kohlhardt M. Single nonselective cation channels and Ca2+-activated K+ channels in aortic endothelial cells. J Membr Biol. 1987;98(2):125–133. doi: 10.1007/BF01872125. [DOI] [PubMed] [Google Scholar]
  11. Filipovic D., Sackin H. A calcium-permeable stretch-activated cation channel in renal proximal tubule. Am J Physiol. 1991 Jan;260(1 Pt 2):F119–F129. doi: 10.1152/ajprenal.1991.260.1.F119. [DOI] [PubMed] [Google Scholar]
  12. Furchgott R. F., Vanhoutte P. M. Endothelium-derived relaxing and contracting factors. FASEB J. 1989 Jul;3(9):2007–2018. [PubMed] [Google Scholar]
  13. 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]
  14. Himmel H. M., Whorton A. R., Strauss H. C. Intracellular calcium, currents, and stimulus-response coupling in endothelial cells. Hypertension. 1993 Jan;21(1):112–127. doi: 10.1161/01.hyp.21.1.112. [DOI] [PubMed] [Google Scholar]
  15. Hoyer J., Popp R., Meyer J., Galla H. J., Gögelein H. Angiotensin II, vasopressin and GTP[gamma-S] inhibit inward-rectifying K+ channels in porcine cerebral capillary endothelial cells. J Membr Biol. 1991 Jul;123(1):55–62. doi: 10.1007/BF01993963. [DOI] [PubMed] [Google Scholar]
  16. Kim D. Novel cation-selective mechanosensitive ion channel in the atrial cell membrane. Circ Res. 1993 Jan;72(1):225–231. doi: 10.1161/01.res.72.1.225. [DOI] [PubMed] [Google Scholar]
  17. Kirber M. T., Ordway R. W., Clapp L. H., Walsh J. V., Jr, Singer J. J. Both membrane stretch and fatty acids directly activate large conductance Ca(2+)-activated K+ channels in vascular smooth muscle cells. FEBS Lett. 1992 Feb 3;297(1-2):24–28. doi: 10.1016/0014-5793(92)80319-c. [DOI] [PubMed] [Google Scholar]
  18. Kirber M. T., Walsh J. V., Jr, Singer J. J. Stretch-activated ion channels in smooth muscle: a mechanism for the initiation of stretch-induced contraction. Pflugers Arch. 1988 Sep;412(4):339–345. doi: 10.1007/BF01907549. [DOI] [PubMed] [Google Scholar]
  19. Lamontagne D., Pohl U., Busse R. Mechanical deformation of vessel wall and shear stress determine the basal release of endothelium-derived relaxing factor in the intact rabbit coronary vascular bed. Circ Res. 1992 Jan;70(1):123–130. doi: 10.1161/01.res.70.1.123. [DOI] [PubMed] [Google Scholar]
  20. Lansman J. B., Hallam T. J., Rink T. J. Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers? 1987 Feb 26-Mar 4Nature. 325(6107):811–813. doi: 10.1038/325811a0. [DOI] [PubMed] [Google Scholar]
  21. Latorre R., Oberhauser A., Labarca P., Alvarez O. Varieties of calcium-activated potassium channels. Annu Rev Physiol. 1989;51:385–399. doi: 10.1146/annurev.ph.51.030189.002125. [DOI] [PubMed] [Google Scholar]
  22. Lew R. A., Baertschi A. J. Endothelial cells stimulate ANF secretion from atrial myocytes in co-culture. Biochem Biophys Res Commun. 1989 Sep 15;163(2):701–709. doi: 10.1016/0006-291x(89)92280-8. [DOI] [PubMed] [Google Scholar]
  23. Lückhoff A., Busse R. Calcium influx into endothelial cells and formation of endothelium-derived relaxing factor is controlled by the membrane potential. Pflugers Arch. 1990 May;416(3):305–311. doi: 10.1007/BF00392067. [DOI] [PubMed] [Google Scholar]
  24. Markwardt F., Isenberg G. Gating of maxi K+ channels studied by Ca2+ concentration jumps in excised inside-out multi-channel patches (myocytes from guinea pig urinary bladder). J Gen Physiol. 1992 Jun;99(6):841–862. doi: 10.1085/jgp.99.6.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mehrke G., Pohl U., Daut J. Effects of vasoactive agonists on the membrane potential of cultured bovine aortic and guinea-pig coronary endothelium. J Physiol. 1991 Aug;439:277–299. doi: 10.1113/jphysiol.1991.sp018667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Morris C. E. Mechanosensitive ion channels. J Membr Biol. 1990 Feb;113(2):93–107. doi: 10.1007/BF01872883. [DOI] [PubMed] [Google Scholar]
  27. Nilius B., Riemann D. Ion channels in human endothelial cells. Gen Physiol Biophys. 1990 Apr;9(2):89–111. [PubMed] [Google Scholar]
  28. Popp R., Hoyer J., Meyer J., Galla H. J., Gögelein H. Stretch-activated non-selective cation channels in the antiluminal membrane of porcine cerebral capillaries. J Physiol. 1992 Aug;454:435–449. doi: 10.1113/jphysiol.1992.sp019272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pácha J., Frindt G., Sackin H., Palmer L. G. Apical maxi K channels in intercalated cells of CCT. Am J Physiol. 1991 Oct;261(4 Pt 2):F696–F705. doi: 10.1152/ajprenal.1991.261.4.F696. [DOI] [PubMed] [Google Scholar]
  30. Ramaciotti C., Sharkey A., McClellan G., Winegrad S. Endothelial cells regulate cardiac contractility. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4033–4036. doi: 10.1073/pnas.89.9.4033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rubanyi G. M., Romero J. C., Vanhoutte P. M. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol. 1986 Jun;250(6 Pt 2):H1145–H1149. doi: 10.1152/ajpheart.1986.250.6.H1145. [DOI] [PubMed] [Google Scholar]
  32. Rusko J., Tanzi F., van Breemen C., Adams D. J. Calcium-activated potassium channels in native endothelial cells from rabbit aorta: conductance, Ca2+ sensitivity and block. J Physiol. 1992 Sep;455:601–621. doi: 10.1113/jphysiol.1992.sp019318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sackin H. A stretch-activated K+ channel sensitive to cell volume. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1731–1735. doi: 10.1073/pnas.86.5.1731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schiebinger R. J., Greening K. M. Interaction between stretch and hormonally stimulated atrial natriuretic peptide secretion. Am J Physiol. 1992 Jan;262(1 Pt 2):H78–H83. doi: 10.1152/ajpheart.1992.262.1.H78. [DOI] [PubMed] [Google Scholar]
  35. Schilling W. P., Elliott S. J. Ca2+ signaling mechanisms of vascular endothelial cells and their role in oxidant-induced endothelial cell dysfunction. Am J Physiol. 1992 Jun;262(6 Pt 2):H1617–H1630. doi: 10.1152/ajpheart.1992.262.6.H1617. [DOI] [PubMed] [Google Scholar]
  36. Schwarz G., Droogmans G., Nilius B. Shear stress induced membrane currents and calcium transients in human vascular endothelial cells. Pflugers Arch. 1992 Jul;421(4):394–396. doi: 10.1007/BF00374230. [DOI] [PubMed] [Google Scholar]
  37. Sigurdson W., Ruknudin A., Sachs F. Calcium imaging of mechanically induced fluxes in tissue-cultured chick heart: role of stretch-activated ion channels. Am J Physiol. 1992 Apr;262(4 Pt 2):H1110–H1115. doi: 10.1152/ajpheart.1992.262.4.H1110. [DOI] [PubMed] [Google Scholar]
  38. Smith J. A., Shah A. M., Lewis M. J. Factors released from endocardium of the ferret and pig modulate myocardial contraction. J Physiol. 1991 Aug;439:1–14. doi: 10.1113/jphysiol.1991.sp018653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Spurr A. R. A low-viscosity epoxy resin embedding medium for electron microscopy. J Ultrastruct Res. 1969 Jan;26(1):31–43. doi: 10.1016/s0022-5320(69)90033-1. [DOI] [PubMed] [Google Scholar]
  40. Takeda K., Schini V., Stoeckel H. Voltage-activated potassium, but not calcium currents in cultured bovine aortic endothelial cells. Pflugers Arch. 1987 Nov;410(4-5):385–393. doi: 10.1007/BF00586515. [DOI] [PubMed] [Google Scholar]
  41. Yang X. C., Sachs F. Block of stretch-activated ion channels in Xenopus oocytes by gadolinium and calcium ions. Science. 1989 Feb 24;243(4894 Pt 1):1068–1071. doi: 10.1126/science.2466333. [DOI] [PubMed] [Google Scholar]

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