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. 1982 Apr 1;79(4):529–547. doi: 10.1085/jgp.79.4.529

Conduction and block by organic cations in a K+-selective channel from sarcoplasmic reticulum incorporated into planar phospholipid bilayers

PMCID: PMC2215483  PMID: 6279756

Abstract

A collection of organic cations has been used to probe the gross structural features of the ionic diffusion pathway in a K+-selective channel from sarcoplasmic reticulum (SR). Channels were incorporated into planar phospholipid bilayer membranes, and single-channel currents were measured in the presence of ammonium-derived cations in the aqueous phases. Small monovalent organic cations are able to permeate the channel: the channel conductance drops sharply for cations having molecular cross sections larger than 18-20 A2. Impermeant or poorly permeant cations such as tetraethylammonium, choline, and glucosamine, among others, block K+ conduction through the channel. This block is voltage dependent and can be described by a one-site, one-ion blocking scheme. 19 monovalent organic cations blocks primarily from the trans side of the membrane (the side defined as zero voltage), and much more weakly, if at all, from the cis side (to which SR vesicles are added). These blockers all appear to interact with a site located at 63% (average value) of the electric potential drop measured from the trans side. Furthermore, block by 1,3-bis[tris(hydroxymethyl)-methylamino] propane (BTP) shows that the presence of a blocking ion increases the duration of the apparent open state, as expected for a scheme in which the blocking site can be reached only when the channel is open. The results lead to a picture of the channel containing a wide (at least 50 A2) nonselective trans entry in series with a narrow (20 A2) constriction.

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Selected References

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  1. Adams P. R. Voltage jump analysis of procaine action at frog end-plate. J Physiol. 1977 Jun;268(2):291–318. doi: 10.1113/jphysiol.1977.sp011858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adelman W. J., Jr, French R. J. Blocking of the squid axon potassium channel by external caesium ions. J Physiol. 1978 Mar;276:13–25. doi: 10.1113/jphysiol.1978.sp012217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Armstrong C. M. Ionic pores, gates, and gating currents. Q Rev Biophys. 1974 May;7(2):179–210. doi: 10.1017/s0033583500001402. [DOI] [PubMed] [Google Scholar]
  4. Armstrong C. M. Potassium pores of nerve and muscle membranes. Membranes. 1975;3:325–358. [PubMed] [Google Scholar]
  5. Bezanilla F., Armstrong C. M. Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons. J Gen Physiol. 1972 Nov;60(5):588–608. doi: 10.1085/jgp.60.5.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coronado R., Miller C. Decamethonium and hexamethonium block K+ channels of sarcoplasmic reticulum. Nature. 1980 Dec 4;288(5790):495–497. doi: 10.1038/288495a0. [DOI] [PubMed] [Google Scholar]
  7. Coronado R., Rosenberg R. L., Miller C. Ionic selectivity, saturation, and block in a K+-selective channel from sarcoplasmic reticulum. J Gen Physiol. 1980 Oct;76(4):425–446. doi: 10.1085/jgp.76.4.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Donovan J. J., Latorre R. Inactivation of the alamethicin-induced conductance caused by quaternary ammonium ions and local anesthetics. J Gen Physiol. 1979 Apr;73(4):425–451. doi: 10.1085/jgp.73.4.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dwyer T. M., Adams D. J., Hille B. The permeability of the endplate channel to organic cations in frog muscle. J Gen Physiol. 1980 May;75(5):469–492. doi: 10.1085/jgp.75.5.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eldefrawi M. E., Aronstam R. S., Bakry N. M., Eldefrawi A. T., Albuquerque E. X. Activation, inactivation, and desensitization of acetylcholine receptor channel complex detected by binding of perhydrohistrionicotoxin. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2309–2313. doi: 10.1073/pnas.77.4.2309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Farley J. M., Yeh J. Z., Watanabe S., Narahashi T. Endplate channel block by guanidine derivatives. J Gen Physiol. 1981 Mar;77(3):273–293. doi: 10.1085/jgp.77.3.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. French R. J., Shoukimas J. J. Blockage of squid axon potassium conductance by internal tetra-N-alkylammonium ions of various sizes. Biophys J. 1981 May;34(2):271–291. doi: 10.1016/S0006-3495(81)84849-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hille B. Ionic selectivity of Na and K channels of nerve membranes. Membranes. 1975;3:255–323. [PubMed] [Google Scholar]
  14. Hille B. Potassium channels in myelinated nerve. Selective permeability to small cations. J Gen Physiol. 1973 Jun;61(6):669–686. doi: 10.1085/jgp.61.6.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hille B., Schwarz W. Potassium channels as multi-ion single-file pores. J Gen Physiol. 1978 Oct;72(4):409–442. doi: 10.1085/jgp.72.4.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hille B. The hydration of sodium ions crossing the nerve membrane. Proc Natl Acad Sci U S A. 1971 Feb;68(2):280–282. doi: 10.1073/pnas.68.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hille B. The permeability of the sodium channel to organic cations in myelinated nerve. J Gen Physiol. 1971 Dec;58(6):599–619. doi: 10.1085/jgp.58.6.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kirsch G. E., Yeh J. Z., Farley J. M., Narahashi T. Interaction of n-alkylguanidines with the sodium channels of squid axon membrane. J Gen Physiol. 1980 Sep;76(3):315–335. doi: 10.1085/jgp.76.3.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koltun W. L. Precision space-filling atomic models. Biopolymers. 1965 Dec;3(6):665–679. doi: 10.1002/bip.360030606. [DOI] [PubMed] [Google Scholar]
  20. Labarca P. P., Miller C. A K+-selective, three-state channel from fragmented sarcoplasmic reticulum of frog leg muscle. J Membr Biol. 1981;61(1):31–38. doi: 10.1007/BF01870750. [DOI] [PubMed] [Google Scholar]
  21. Labarca P., Coronado R., Miller C. Thermodynamic and kinetic studies of the gating behavior of a K+-selective channel from the sarcoplasmic reticulum membrane. J Gen Physiol. 1980 Oct;76(4):397–324. doi: 10.1085/jgp.76.4.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lo M. V., Shrager P. Block and inactivation of sodium channels in nerve by amino acid derivatives. II. Dependence on temperature and drug concentration. Biophys J. 1981 Jul;35(1):45–57. doi: 10.1016/S0006-3495(81)84773-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McKinley D., Meissner G. Evidence for a K+, Na+ permeable channel in sarcoplasmic reticulum. J Membr Biol. 1978 Dec 15;44(2):159–186. doi: 10.1007/BF01976037. [DOI] [PubMed] [Google Scholar]
  24. Miller C., Rosenberg R. L. A voltage-gated cation conductance channel from fragmented sarcoplasmic reticulum. Effects of transition metal ions. Biochemistry. 1979 Apr 3;18(7):1138–1145. doi: 10.1021/bi00574a003. [DOI] [PubMed] [Google Scholar]
  25. Miller C. Voltage-gated cation conductance channel from fragmented sarcoplasmic reticulum: steady-state electrical properties. J Membr Biol. 1978 Apr 20;40(1):1–23. doi: 10.1007/BF01909736. [DOI] [PubMed] [Google Scholar]
  26. Moreno J. H., Diamond J. M. Cation permeation mechanisms and cation selectivity in "tight junctions" of gallbladder epithelium. Membranes. 1975;3:383–497. [PubMed] [Google Scholar]
  27. 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]
  28. Rojas E., Rudy B. Destruction of the sodium conductance inactivation by a specific protease in perfused nerve fibres from Loligo. J Physiol. 1976 Nov;262(2):501–531. doi: 10.1113/jphysiol.1976.sp011608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ruff R. L. A quantitative analysis of local anaesthetic alteration of miniature end-plate currents and end-plate current fluctuations. J Physiol. 1977 Jan;264(1):89–124. doi: 10.1113/jphysiol.1977.sp011659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Swenson R. P., Jr Inactivation of potassium current in squid axon by a variety of quaternary ammonium ions. J Gen Physiol. 1981 Mar;77(3):255–271. doi: 10.1085/jgp.77.3.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Watanabe S., Narahashi T. Cation selectivity of acetylcholine-activated ionic channel of frog endplate. J Gen Physiol. 1979 Nov;74(5):615–628. doi: 10.1085/jgp.74.5.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. White M. M., Miller C. Probes of the conduction process of a voltage-gated Cl- channel from Torpedo electroplax. J Gen Physiol. 1981 Jul;78(1):1–18. doi: 10.1085/jgp.78.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]

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