Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1998 Feb;74(2 Pt 1):722–730. doi: 10.1016/S0006-3495(98)73997-9

External action of di- and polyamines on maxi calcium-activated potassium channels: an electrophysiological and molecular modeling study.

T M Weiger 1, T Langer 1, A Hermann 1
PMCID: PMC1302553  PMID: 9533685

Abstract

In this study we compared polyamines to various diamines, and we modeled flexibility as well as hydrophobicity properties of these molecules to examine possible structural differences that could explain their external effects on the channels. The natural polyamines (putrescine, cadaverine, spermidine, spermine) and diamines increasing in CH2 chain length from C2 to C12 were used to probe maxi calcium-activated potassium (BK) channels in GH3 pituitary tumor cells when applied extracellularly. In single-channel recordings we found polyamines as well as diamines up to 1,10-diaminodecane to be ineffective in altering channel current amplitudes or kinetics. In contrast, 1,12-diamino dodecane (1,12-DD) was found to be a reversible blocker, with a blocking site at an electrical distance (z delta) of 0.72 within the channel. It reduced single-channel current amplitude, mean channel open time, and channel open probability. In computer simulations structural data, such as flexibility, hydration, and log D values, were calculated. 1,12-DD showed the largest flexibility of all diamines (minimum N-N distance 9.9 A) combined with a marked hydrophobicity due to a 4-5 A hydrophobic intersegment between hydrophilic ends in the molecule, as confirmed by GRID water probe maps and a log D value of -1.82 at pH 7.2. We propose that the amount of hydration of the molecule, more than its flexibility, constitutes an essential parameter for its ability to act as a channel blocker.

Full Text

The Full Text of this article is available as a PDF (506.1 KB).

Selected References

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

  1. Armstrong C. M. Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. J Gen Physiol. 1971 Oct;58(4):413–437. doi: 10.1085/jgp.58.4.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blatz A. L., Magleby K. L. Ion conductance and selectivity of single calcium-activated potassium channels in cultured rat muscle. J Gen Physiol. 1984 Jul;84(1):1–23. doi: 10.1085/jgp.84.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bokvist K., Rorsman P., Smith P. A. Block of ATP-regulated and Ca2(+)-activated K+ channels in mouse pancreatic beta-cells by external tetraethylammonium and quinine. J Physiol. 1990 Apr;423:327–342. doi: 10.1113/jphysiol.1990.sp018025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bondy S. C., Walker C. H. Polyamines contribute to calcium-stimulated release of aspartate from brain particulate fractions. Brain Res. 1986 Apr 16;371(1):96–100. doi: 10.1016/0006-8993(86)90814-0. [DOI] [PubMed] [Google Scholar]
  5. Copello J., Segal Y., Reuss L. Cytosolic pH regulates maxi K+ channels in Necturus gall-bladder epithelial cells. J Physiol. 1991 Mar;434:577–590. doi: 10.1113/jphysiol.1991.sp018487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cornejo M., Guggino S. E., Guggino W. B. Ca2+-activated K+ channels from cultured renal medullary thick ascending limb cells: effects of pH. J Membr Biol. 1989 Aug;110(1):49–55. doi: 10.1007/BF01870992. [DOI] [PubMed] [Google Scholar]
  7. Drouin H., Hermann A. Intracellular action of spermine on neuronal Ca2+ and K+ currents. Eur J Neurosci. 1994 Mar 1;6(3):412–419. doi: 10.1111/j.1460-9568.1994.tb00284.x. [DOI] [PubMed] [Google Scholar]
  8. Dufourcq J., Clin B., Lemanceau B. NMR Study of ganglion-blocking and curare-like dimethoniums conformation in aqueous solutions. FEBS Lett. 1972 May 1;22(2):205–209. doi: 10.1016/0014-5793(72)80046-2. [DOI] [PubMed] [Google Scholar]
  9. Fakler B., Brändle U., Glowatzki E., Weidemann S., Zenner H. P., Ruppersberg J. P. Strong voltage-dependent inward rectification of inward rectifier K+ channels is caused by intracellular spermine. Cell. 1995 Jan 13;80(1):149–154. doi: 10.1016/0092-8674(95)90459-x. [DOI] [PubMed] [Google Scholar]
  10. Ficker E., Taglialatela M., Wible B. A., Henley C. M., Brown A. M. Spermine and spermidine as gating molecules for inward rectifier K+ channels. Science. 1994 Nov 11;266(5187):1068–1072. doi: 10.1126/science.7973666. [DOI] [PubMed] [Google Scholar]
  11. Gomez M., Hellstrand P. Effects of polyamines on voltage-activated calcium channels in guinea-pig intestinal smooth muscle. Pflugers Arch. 1995 Aug;430(4):501–507. doi: 10.1007/BF00373886. [DOI] [PubMed] [Google Scholar]
  12. Goodford P. J. A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. J Med Chem. 1985 Jul;28(7):849–857. doi: 10.1021/jm00145a002. [DOI] [PubMed] [Google Scholar]
  13. Gray M. A., Tomlins B., Montgomery R. A., Williams A. J. Structural aspects of the sarcoplasmic reticulum K+ channel revealed by gallamine block. Biophys J. 1988 Aug;54(2):233–239. doi: 10.1016/S0006-3495(88)82952-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hermann A., Gorman A. L. Effects of tetraethylammonium on potassium currents in a molluscan neurons. J Gen Physiol. 1981 Jul;78(1):87–110. doi: 10.1085/jgp.78.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lang D. G., Ritchie A. K. Tetraethylammonium blockade of apamin-sensitive and insensitive Ca2(+)-activated K+ channels in a pituitary cell line. J Physiol. 1990 Jun;425:117–132. doi: 10.1113/jphysiol.1990.sp018095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miller C. Bis-quaternary ammonium blockers as structural probes of the sarcoplasmic reticulum K+ channel. J Gen Physiol. 1982 May;79(5):869–891. doi: 10.1085/jgp.79.5.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Neher E., Steinbach J. H. Local anaesthetics transiently block currents through single acetylcholine-receptor channels. J Physiol. 1978 Apr;277:153–176. doi: 10.1113/jphysiol.1978.sp012267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Neyton J., Miller C. Discrete Ba2+ block as a probe of ion occupancy and pore structure in the high-conductance Ca2+ -activated K+ channel. J Gen Physiol. 1988 Nov;92(5):569–586. doi: 10.1085/jgp.92.5.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nomura K., Naruse K., Watanabe K., Sokabe M. Aminoglycoside blockade of Ca2(+)-activated K+ channel from rat brain synaptosomal membranes incorporated into planar bilayers. J Membr Biol. 1990 May;115(3):241–251. doi: 10.1007/BF01868639. [DOI] [PubMed] [Google Scholar]
  20. Pajunen A. E., Hietala O. A., Virransalo E. L., Piha R. S. Ornithine decarboxylase and adenosylmethionine decarboxylase in mouse brain--effect of electrical stimulation. J Neurochem. 1978 Jan;30(1):281–283. doi: 10.1111/j.1471-4159.1978.tb07066.x. [DOI] [PubMed] [Google Scholar]
  21. Pegg A. E., McCann P. P. Polyamine metabolism and function. Am J Physiol. 1982 Nov;243(5):C212–C221. doi: 10.1152/ajpcell.1982.243.5.C212. [DOI] [PubMed] [Google Scholar]
  22. Pegg A. E. Recent advances in the biochemistry of polyamines in eukaryotes. Biochem J. 1986 Mar 1;234(2):249–262. doi: 10.1042/bj2340249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rock D. M., Macdonald R. L. Polyamine regulation of N-methyl-D-aspartate receptor channels. Annu Rev Pharmacol Toxicol. 1995;35:463–482. doi: 10.1146/annurev.pa.35.040195.002335. [DOI] [PubMed] [Google Scholar]
  24. Romano C., Williams K., DePriest S., Seshadri R., Marshall G. R., Israel M., Molinoff P. B. Effects of mono-, di-, and triamines on the N-methyl-D-aspartate receptor complex: a model of the polyamine recognition site. Mol Pharmacol. 1992 Apr;41(4):785–792. [PubMed] [Google Scholar]
  25. Scott R. H., Sutton K. G., Dolphin A. C. Interactions of polyamines with neuronal ion channels. Trends Neurosci. 1993 Apr;16(4):153–160. doi: 10.1016/0166-2236(93)90124-5. [DOI] [PubMed] [Google Scholar]
  26. Tabor C. W., Tabor H. Polyamines. Annu Rev Biochem. 1984;53:749–790. doi: 10.1146/annurev.bi.53.070184.003533. [DOI] [PubMed] [Google Scholar]
  27. Villarroel A., Alvarez O., Oberhauser A., Latorre R. Probing a Ca2+-activated K+ channel with quaternary ammonium ions. Pflugers Arch. 1988 Dec;413(2):118–126. doi: 10.1007/BF00582521. [DOI] [PubMed] [Google Scholar]
  28. Weiger T., Hermann A. Polyamines block Ca(2+)-activated K+ channels in pituitary tumor cells (GH3). J Membr Biol. 1994 Jun;140(2):133–142. doi: 10.1007/BF00232901. [DOI] [PubMed] [Google Scholar]
  29. Woodhull A. M. Ionic blockage of sodium channels in nerve. J Gen Physiol. 1973 Jun;61(6):687–708. doi: 10.1085/jgp.61.6.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yellen G. Ionic permeation and blockade in Ca2+-activated K+ channels of bovine chromaffin cells. J Gen Physiol. 1984 Aug;84(2):157–186. doi: 10.1085/jgp.84.2.157. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES