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Permeation and selectivity in calcium channels.
William A Sather1, Edwin W McCleskey
1Department of Pharmacology, University of Colorado Health Science Center, Denver, Colorado 80262-5426, USA. william.sather@uchsc.edu
Annual Review of Physiology
|December 10, 2002
Summary
Calcium channels achieve high selectivity using flexible glutamate residues, unlike rigid potassium channels. This unique structure allows selective calcium ion passage while blocking sodium.
Area of Science:
- Molecular Biology
- Biophysics
- Ion Channel Physiology
Background:
- Potassium (K+) channels utilize rigid pores and carbonyl oxygens for ion selectivity.
- Calcium (Ca2+) channels exhibit exceptional selectivity and high flux, a mechanism distinct from K+ channels.
Purpose of the Study:
- To review experimental and theoretical advances in understanding Ca2+ channel structure and function.
- To elucidate the structural basis for Ca2+ channel selectivity and permeation.
Main Methods:
- Review of experimental evidence from various studies.
- Analysis of theoretical models explaining Ca2+ channel mechanisms.
Main Results:
- Ca2+ channels employ four glutamate residues (EEEE locus) with flexible carboxyl side chains in the pore.
- The pore structure is flexible, binding single Ca2+ ions to block Na+ and multiple Ca2+ ions for flux.
- Non-equivalence of the four glutamate residues is crucial for Ca2+ permeation.
Conclusions:
- Ca2+ channel selectivity arises from flexible glutamate interactions, differing significantly from K+ channel structures.
- The flexible pore mechanism explains the simultaneous high selectivity and high flux characteristic of Ca2+ channels.