Abstract
The mechanism by which ions deliver their message to effector proteins involves a change in the protein conformation which is induced by the specific interaction of the ion with its binding site on the protein. In the case of an ion-channel protein, conforma-tional changes induced by permeant ions and the consequences for channel function have received little attention. Here we report that binding of permeant cations to an intra-channel binding site of the dihydropyridine (DHP)-sensitive (L-type) Ca2+ channel leads to a conformational change which destabilizes the protonated state of a group on the external channel surface, and can shift its apparent pK value by more than 2 pH units. The lifetime of the protonated state correlates with the occupancy of an intra-channel binding site by the permeant cation. The demonstration of such conformational changes in a channel protein induced by the permeant ion has important implications for realistic models of the mechanism of ion permeation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Prod'hom, B., Pietrobon, D. & Hess, P. Nature 329, 243–246 (1987).
Hof, R. P., Ruegg, U. T., Hof, A. & Vogel, A. J. Cardiovascular Pharmac. 7, 689–693 (1985).
Kokubun, S., Prod'hom, B., Becker, C., Porzig, H. & Reuter H. Molec. Pharmac. 30: 571–584 (1986).
Vereeke, J. & Carmeliet, R. B. Pflügers Arch. ges. Physiol. 322, 73–82 (1971).
Hagiwara, S., Fukuda, J. & Eaton, D. C. J. gen. Physiol. 63, 564–578 (1974).
Kostyuk, P. G., Mironov, S. L. & Shuba, Y. M. J. Membrane Biol. 76, 83–93 (1983).
Hess, P. & Tsien, R. W. Nature 309, 453–456 (1984).
Almers, W. & McCleskey, E. W. J. Physiol., Lond. 353, 585–608 (1984).
Coronado, R. & Smith J. S. Biophys. J. 51, 497–502 (1987).
Hess, P., Lansman, J. B. & Tsien, R. W. J. gen. Physiol. 88, 293–319 (1986).
Lansman, J. B., Hess, P. & Tsien, R. W. J. gen. Physiol. 88, 321–347 (1986).
Warshel, A. Nature 330, 15–16 (1987).
Eisenman, G., Sandblom, J. P. & Walker, J. L. Jr. Science 155, 965–974 (1967).
Neher, E. Biochim. biophys. Acta 401, 540–544 (1975).
Hagiwara, S., Miyazaki, S., Krasne, S. & Ciani, S. J. gen. Physiol. 70, 269–281 (1977).
Urban, B. W., Hladky, S. B. & Haydon, D. A. Fedn Proc. 37, 2628–2632 (1978).
Hille, B. & Schwarz, W. J. gen. Physiol. 11, 409–442 (1978).
Ciani, S. Biophys. J. 46, 249–252 (1984).
Lauger, P. Biophys. J. 47, 581–591 (1985).
Hamill, O., Marty, A., Neher, E., Sakmann, B., & Sigworth, F. J. Pflügers Arch. ges. Physiol. 391, 85–100 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pietrobon, D., Prod'hom, B. & Hess, P. Conformational changes associated with ion permeation in L-type calcium channels. Nature 333, 373–376 (1988). https://doi.org/10.1038/333373a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/333373a0
- Springer Nature Limited
This article is cited by
-
Cinnamaldehyde inhibits L-type calcium channels in mouse ventricular cardiomyocytes and vascular smooth muscle cells
Pflügers Archiv - European Journal of Physiology (2014)
-
Ion-conformational interaction and charge transport through channels of biological membranes
Journal of Biological Physics (1993)
-
Effects of irreversible and reversible cholinesterase inhibitors on single acetylcholine-activated channels
The Journal of Membrane Biology (1992)
-
Developmental changes in the calcium currents in embryonic chick ventricular myocytes
The Journal of Membrane Biology (1991)
-
Patch-clamp studies on the anomalous mole fraction effect of the K+ channel in cytoplasmic droplets ofNitella: An attempt to distinguish between a multi-ion single-file pore and an enzyme kinetic model with lazy state
The Journal of Membrane Biology (1991)