Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel

Science

Volumn 271, Issue 5249, 1996, Pages 653-656

  Baukrowitz, Thomas ^a   Yellen, Gary ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

POTASSIUM CHANNEL; POTASSIUM ION; QUATERNARY AMMONIUM DERIVATIVE;

ANIMAL CELL; ARTICLE; CONFORMATIONAL TRANSITION; DROSOPHILA; MAMMAL CELL; NONHUMAN; POTASSIUM TRANSPORT; PRIORITY JOURNAL;

ANIMALIA; MAMMALIA;

EID: 0030031856     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.271.5249.653     Document Type: Article

References (34)

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2. R. L. Macdonald, Epilepsia 30, S19 (1989); J T. Bigger and B. F Hoffman, in The Pharmacological Basis of Therapeutics, A G. Gilman, L S. Goodman, R. W. Rail, F. Murad, Eds. (Macmillan, New York, 1985), chap. 31.
3. The two accepted models for use-dependent blockade erther use an increased affinity of the binding site in the open or inactivated state (the "modulated receptor" model) or trap the blocker in the channel by a closed gate (the "guarded receptor" model) [B. Hille, J. Gen. Physiol. 69, 497 (1977); C. F. Starmer, A. O. Grant, H. C Strauss, Biophys. J. 46, 15 (1984); J F Butterworth and G. R. Strichartz, Anesthesiology 72, 711 (1990)].
4. The two accepted models for use-dependent blockade erther use an increased affinity of the binding site in the open or inactivated state (the "modulated receptor" model) or trap the blocker in the channel by a closed gate (the "guarded receptor" model) [B. Hille, J. Gen. Physiol. 69, 497 (1977); C. F. Starmer, A. O. Grant, H. C Strauss, Biophys. J. 46, 15 (1984); J F Butterworth and G. R. Strichartz, Anesthesiology 72, 711 (1990)].
5. The two accepted models for use-dependent blockade erther use an increased affinity of the binding site in the open or inactivated state (the "modulated receptor" model) or trap the blocker in the channel by a closed gate (the "guarded receptor" model) [B. Hille, J. Gen. Physiol. 69, 497 (1977); C. F. Starmer, A. O. Grant, H. C Strauss, Biophys. J. 46, 15 (1984); J F Butterworth and G. R. Strichartz, Anesthesiology 72, 711 (1990)].
6. 2-terminal portion of the protein acts as a tethered blocker to inactivate the channel [T. Hoshi, W. N. Zagotta, R. W. Aldrich, Science 250, 533 (1990); S D Demo and G. Yelten, Neuron 7, 743 (1991)]
7. 2-terminal portion of the protein acts as a tethered blocker to inactivate the channel [T. Hoshi, W. N. Zagotta, R. W. Aldrich, Science 250, 533 (1990); S D Demo and G. Yelten, Neuron 7, 743 (1991)]
8. K L. Choi, R. W. Aldnch, G. Yellen, Proc. Natl. Acad. Sci. U.S.A 88, 5092 (1991).
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10. T. Hoshi, W. N. Zagotta, R. W Aldrich, Neuron 7, 547 (1991); G Yellen, D. Sodickson, T.-Y. Chen, M. E. Jurman, Biophys J 66, 1068 (1994).
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12. 2n+1)triethylammonium, Br, bretylium; and QX, QX-314 (a quaternary lidocaine derivative with a triethylamino moiety)
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14. T. Baukrowitz and G. Yellen, ibid. 15, 951 (1995).
15. + measured in either the presence or the absence of blocker (so long as there was no outward flux).
16. + measured in either the presence or the absence of blocker (so long as there was no outward flux).
17. + measured in either the presence or the absence of blocker (so long as there was no outward flux).
18. + measured in either the presence or the absence of blocker (so long as there was no outward flux).
19. + measured in either the presence or the absence of blocker (so long as there was no outward flux).
20. B. Hille, Ionic Channels of Excitable Membranes (Sinauer, Sunderland, MA, ed. 2, 1992), chap. 11; J. Crank, The Mathematics of Diffusion (Clarendon Press, Oxford, UK, ed. 2, 1975).
21. B. Hille, Ionic Channels of Excitable Membranes (Sinauer, Sunderland, MA, ed. 2, 1992), chap. 11; J. Crank, The Mathematics of Diffusion (Clarendon Press, Oxford, UK, ed. 2, 1975).
22. + made no detectable difference (9, T. Baukrowitz and G. Yellen, unpublished data).
23. A. L. Hodgkin and R. D. Keynes, J. Physiol (London) 128, 61 (1955); B. Hille and W. Schwarz, J. Gen. Physiol. 72, 409 (1978)
24. A. L. Hodgkin and R. D. Keynes, J. Physiol (London) 128, 61 (1955); B. Hille and W. Schwarz, J. Gen. Physiol. 72, 409 (1978)
25. W. Almers and E. W McCleskey, J. Physiol (London) 353, 585 (1984); P. Hess and R. W. Tsien, Nature 309, 453 (1984).
26. W. Almers and E. W McCleskey, J. Physiol (London) 353, 585 (1984); P. Hess and R. W. Tsien, Nature 309, 453 (1984).
27. + ion remaining: It could be that of the penultimate ion, for example, but not that of the first ion to leave (which must proceed at the rate of permeation)
28. T Baukrowitz and G. Yellen, data not shown
29. L M Hondeghem and D J. Snyders, Circulation 81, 686 (1990); but see T. J. Colatsky, C. H. Follmer, C. F. Starmer, ibid. 82, 2235 (1990).
30. L M Hondeghem and D J. Snyders, Circulation 81, 686 (1990); but see T. J. Colatsky, C. H. Follmer, C. F. Starmer, ibid. 82, 2235 (1990).
31. 2, and 10 mM Hepes (pH 7.4), in which KCl was substituted for NMG as indicated.
32. Copper (ll):phenanthroline (750 μM:3 mM) was applied to the intracellular face of the patch for < 1 min to eliminate N-type inactivation [J. P. Ruppersberg et al, Nature 352, 711 (1991)]
33. Power spectra from long pulses were computed by fast Founer transform (Matlab; Mathsoft, Natick, MA) and fitted to a sum of Lorentzian and 1/f noise, where f is the frequency The corner frequency and fractional block were used to compute the off-rate of the blocker
34. We thank M. Jurman for providing transfected cells and C Miller for his trenchant advice on the manuscript. Supported by National Institute of Neurological Diseases and Stroke grant NS29693 (G.Y.) and by a stipend from the Gottlieb Daimler - Karl Benz Foundation (T.B.).