Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Jan;117(1):35–42. doi: 10.1111/j.1476-5381.1996.tb15151.x

Discrimination between subtypes of apamin-sensitive Ca(2+)-activated K+ channels by gallamine and a novel bis-quaternary quinolinium cyclophane, UCL 1530.

P M Dunn 1, D C Benton 1, J Campos Rosa 1, C R Ganellin 1, D H Jenkinson 1
PMCID: PMC1909372  PMID: 8825340

Abstract

1. Gallamine, dequalinium and a novel bis-quaternary cyclophane, UCL 1530 (8,19-diaza-3(1,4),5(1,4)-dibenzena-1 (1,4),7(1,4)-diquinolina-cyclononadecanephanedium) were tested for their ability to block actions mediated by the small conductance, apamin-sensitive Ca(2+)-activated K+ (SKCa) channels in rat cultured sympathetic neurones and guinea-pig isolated hepatocytes. 2. SKCa channel block was assessed in sympathetic neurones by the reduction in the slow afterhyperpolarization (AHP) that follows an action potential, and in hepatocytes by the inhibition of the SKCa mediated net loss of K+ that results from the application of angiotensin II. 3. The order of potency for inhibition of the AHP in sympathetic neurones was UCL 1530 > dequalinium > gallamine, with IC50 values of 0.08 +/- 0.02, 0.60 +/- 0.05 and 68.0 +/- 8.4 microM respectively, giving an equi-effective molar ratio between gallamine and UCL 1530 of 850. 4. The same three compounds inhibited angiotensin II-evoked K+ loss from guinea-pig hepatocytes in the order dequalinium > UCL 1530 > gallamine, with an equi-effective molar ratio for gallamine to UCL 1530 of 5.8, 150 fold less than in sympathetic neurones. 5. Dequalinium and UCL 1530 were as effective on guinea-pig as on rat sympathetic neurones. 6. UCL 1530 at 1 microM had no effect on the voltage-activated Ca2+ current in rat sympathetic neurones, but inhibited the hyperpolarization produced by direct elevation of cytosolic Ca2+. 7. Direct activation of SKCa channels by raising cytosolic Ca2+ in hepatocytes evoked an outward current which was reduced by the three blockers, with dequalinium being the most potent. 8. These results provide evidence that the SKCa channels present in guinea-pig hepatocytes and rat cultured sympathetic neurones are different, and that this is not attributable to species variation. UCL 1530 and gallamine should be useful tools for the investigation of subtypes of apamin-sensitive K+ channels.

Full text

PDF
41

Selected References

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

  1. 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]
  2. Bourque C. W., Brown D. A. Apamin and d-tubocurarine block the afterhyperpolarization of rat supraoptic neurosecretory neurons. Neurosci Lett. 1987 Nov 23;82(2):185–190. doi: 10.1016/0304-3940(87)90127-3. [DOI] [PubMed] [Google Scholar]
  3. Burgess G. M., Claret M., Jenkinson D. H. Effects of quinine and apamin on the calcium-dependent potassium permeability of mammalian hepatocytes and red cells. J Physiol. 1981 Aug;317:67–90. doi: 10.1113/jphysiol.1981.sp013814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Capiod T., Field A. C., Ogden D. C., Sandford C. A. Internal perfusion of guinea-pig hepatocytes with buffered Ca2+ or inositol 1,4,5-trisphosphate mimics noradrenaline activation of K+ and Cl- conductances. FEBS Lett. 1987 Jun 15;217(2):247–252. doi: 10.1016/0014-5793(87)80672-5. [DOI] [PubMed] [Google Scholar]
  5. Capiod T., Ogden D. C. The properties of calcium-activated potassium ion channels in guinea-pig isolated hepatocytes. J Physiol. 1989 Feb;409:285–295. doi: 10.1113/jphysiol.1989.sp017497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Castle N. A., Haylett D. G., Morgan J. M., Jenkinson D. H. Dequalinium: a potent inhibitor of apamin-sensitive K+ channels in hepatocytes and of nicotinic responses in skeletal muscle. Eur J Pharmacol. 1993 May 19;236(2):201–207. doi: 10.1016/0014-2999(93)90590-e. [DOI] [PubMed] [Google Scholar]
  7. Colquhoun D., Rang H. P., Ritchie J. M. The binding of tetrodotoxin and alpha-bungarotoxin to normal and denervated mammalian muscle. J Physiol. 1974 Jul;240(1):199–226. doi: 10.1113/jphysiol.1974.sp010607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cook N. S., Haylett D. G. Effects of apamin, quinine and neuromuscular blockers on calcium-activated potassium channels in guinea-pig hepatocytes. J Physiol. 1985 Jan;358:373–394. doi: 10.1113/jphysiol.1985.sp015556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dunn P. M. Dequalinium, a selective blocker of the slow afterhyperpolarization in rat sympathetic neurones in culture. Eur J Pharmacol. 1994 Feb 3;252(2):189–194. doi: 10.1016/0014-2999(94)90596-7. [DOI] [PubMed] [Google Scholar]
  10. Field A. C., Jenkinson D. H. The effect of noradrenaline on the ion permeability of isolated mammalian hepatocytes, studied by intracellular recording. J Physiol. 1987 Nov;392:493–512. doi: 10.1113/jphysiol.1987.sp016793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Freschi J. E. Membrane currents of cultured rat sympathetic neurons under voltage clamp. J Neurophysiol. 1983 Dec;50(6):1460–1478. doi: 10.1152/jn.1983.50.6.1460. [DOI] [PubMed] [Google Scholar]
  12. Grissmer S., Lewis R. S., Cahalan M. D. Ca(2+)-activated K+ channels in human leukemic T cells. J Gen Physiol. 1992 Jan;99(1):63–84. doi: 10.1085/jgp.99.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Habermann E. Apamin. Pharmacol Ther. 1984;25(2):255–270. doi: 10.1016/0163-7258(84)90046-9. [DOI] [PubMed] [Google Scholar]
  14. Hall J. M., Morton I. K. Bradykinin B2 receptor evoked K+ permeability increase mediates relaxation in the rat duodenum. Eur J Pharmacol. 1991 Feb 7;193(2):231–238. doi: 10.1016/0014-2999(91)90041-n. [DOI] [PubMed] [Google Scholar]
  15. Hugues M., Romey G., Duval D., Vincent J. P., Lazdunski M. Apamin as a selective blocker of the calcium-dependent potassium channel in neuroblastoma cells: voltage-clamp and biochemical characterization of the toxin receptor. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1308–1312. doi: 10.1073/pnas.79.4.1308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Konnerth A., Lux H. D., Morad M. Proton-induced transformation of calcium channel in chick dorsal root ganglion cells. J Physiol. 1987 May;386:603–633. doi: 10.1113/jphysiol.1987.sp016553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koumi S., Sato R., Aramaki T. Characterization of the calcium-activated chloride channel in isolated guinea-pig hepatocytes. J Gen Physiol. 1994 Aug;104(2):357–373. doi: 10.1085/jgp.104.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Leinders T., Vijverberg H. P. Ca2+ dependence of small Ca(2+)-activated K+ channels in cultured N1E-115 mouse neuroblastoma cells. Pflugers Arch. 1992 Dec;422(3):223–232. doi: 10.1007/BF00376206. [DOI] [PubMed] [Google Scholar]
  20. Maas A. J., Den Hertog A., Ras R., Van den Akker J. The action of apamin on guinea-pig taenia caeci. Eur J Pharmacol. 1980 Oct 17;67(2-3):265–274. doi: 10.1016/0014-2999(80)90507-5. [DOI] [PubMed] [Google Scholar]
  21. Marquèze B., Seagar M. J., Couraud F. Photoaffinity labeling of the K+-channel-associated apamin-binding molecule in smooth muscle, liver and heart membranes. Eur J Biochem. 1987 Dec 1;169(2):295–298. doi: 10.1111/j.1432-1033.1987.tb13611.x. [DOI] [PubMed] [Google Scholar]
  22. McAfee D. A., Yarowsky P. J. Calcium-dependent potentials in the mammalian sympathetic neurone. J Physiol. 1979 May;290(2):507–523. doi: 10.1113/jphysiol.1979.sp012787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McKillen H. C., Davies N. W., Stanfield P. R., Standen N. B. The effect of intracellular anions on ATP-dependent potassium channels of rat skeletal muscle. J Physiol. 1994 Sep 15;479(Pt 3):341–351. doi: 10.1113/jphysiol.1994.sp020300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Park Y. B. Ion selectivity and gating of small conductance Ca(2+)-activated K+ channels in cultured rat adrenal chromaffin cells. J Physiol. 1994 Dec 15;481(Pt 3):555–570. doi: 10.1113/jphysiol.1994.sp020463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schmid-Antomarchi H., Hugues M., Lazdunski M. Properties of the apamin-sensitive Ca2+-activated K+ channel in PC12 pheochromocytoma cells which hyper-produce the apamin receptor. J Biol Chem. 1986 Jul 5;261(19):8633–8637. [PubMed] [Google Scholar]
  26. Schmid-Antomarchi H., Hugues M., Norman R., Ellory C., Borsotto M., Lazdunski M. Molecular properties of the apamin-binding component of the Ca2+-dependent K+ channel. Radiation-inactivation, affinity labelling and solubilization. Eur J Biochem. 1984 Jul 2;142(1):1–6. doi: 10.1111/j.1432-1033.1984.tb08242.x. [DOI] [PubMed] [Google Scholar]
  27. Seglen P. O. Preparation of rat liver cells. II. Effects of ions and chelators on tissue dispersion. Exp Cell Res. 1973 Jan;76(1):25–30. doi: 10.1016/0014-4827(73)90414-x. [DOI] [PubMed] [Google Scholar]
  28. Smart T. G. Single calcium-activated potassium channels recorded from cultured rat sympathetic neurones. J Physiol. 1987 Aug;389:337–360. doi: 10.1113/jphysiol.1987.sp016660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Takanashi H., Sawanobori T., Kamisaka K., Maezawa H., Hiraoka M. Ca(2+)-activated K+ channel is present in guinea-pig but lacking in rat hepatocytes. Jpn J Physiol. 1992;42(3):415–430. doi: 10.2170/jjphysiol.42.415. [DOI] [PubMed] [Google Scholar]
  30. Wadsworth J. D., Doorty K. B., Strong P. N. Comparable 30-kDa apamin binding polypeptides may fulfill equivalent roles within putative subtypes of small conductance Ca(2+)-activated K+ channels. J Biol Chem. 1994 Jul 8;269(27):18053–18061. [PubMed] [Google Scholar]
  31. Zhang L., Weiner J. L., Valiante T. A., Velumian A. A., Watson P. L., Jahromi S. S., Schertzer S., Pennefather P., Carlen P. L. Whole-cell recording of the Ca(2+)-dependent slow afterhyperpolarization in hippocampal neurones: effects of internally applied anions. Pflugers Arch. 1994 Feb;426(3-4):247–253. doi: 10.1007/BF00374778. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES