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Mutations at two distinct sites within the channel domain M2 alter calcium permeability of neuronal alpha 7 nicotinic receptor.
Open accessAbstract
The relative permeability for sodium, potassium, and calcium of chicken alpha 7 neuronal nicotinic receptor was investigated by mutagenesis of the channel domain M2. Mutations in the "intermediate ring" of negatively charged residues, located at the cytoplasmic end of M2 (site 1), reduce calcium permeability without significantly modifying other functional properties (activation and desensitization) of the receptor; a similar change of ion selectivity is also noticed when mutations at site 1 are done in the context of a receptor mutant that conducts ions in a desensitized state. Moreover, mutations of two adjacent rings of leucines at the synaptic end of M2 (site 2) have multiple effects. They abolish calcium permeability, increase the apparent affinity for acetylcholine by 10- to 100-fold, augment Hill numbers (up to 4.6-5.0) of acetylcholine dose-response relationships, slow rates of ionic response onset, and lower the extent of desensitization. Mutations at these two topographically distinct sites within M2 selectively alter calcium transport without affecting the relative permeabilities for sodium and potassium.
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Citations
Cited by
Nicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System
Dani, J. A., & Bertrand, D. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105214 · Cited by 1,197
Self-citationNicotinic Receptors in the Development and Modulation of CNS Synapses
Role, L. W., & Berg, D. K. (1996) · Neuron · doi:10.1016/s0896-6273(00)80134-8 · Cited by 762
Albuquerque, E. X., Alkondon, M., Pereira, E. F. R., Castro, N. G., Schrattenholz, A., Barbosa, C. T. F., Bonfante-Cabarcas, R., Aracava, Y., Eisenberg, H. M., & Maelicke, A. (1997) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36503-6 · Cited by 445
Steinlein, O. K., Magnusson, A., Stoodt, J., Bertrand, S., Weiland, S., Berkovic, S. F., Nakken, K. O., Propping, P., & Bertrand, D. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.6.943 · Cited by 357
Self-citationβ-Amyloid peptide blocks the response of α7-containing nicotinic receptors on hippocampal neurons
Liu, Q.-S., Kawai, H., & Berg, D. K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081553598 · Cited by 331
Metadata
- Authors
- Bertrand, D., Galzi, J. L., Devillers-Thiéry, A., Bertrand, S., & Changeux, J. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1993-08
- Volume
- 90
- Issue
- 15
- Pages
- 6971-6975
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1964737820
- Cited by
- 391
- References
- 0
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Bertrand, D., Galzi, J. L., Devillers-Thiéry, A., Bertrand, S., & Changeux, J. P. (1993). Mutations at two distinct sites within the channel domain M2 alter calcium permeability of neuronal alpha 7 nicotinic receptor. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.90.15.6971
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