Differential contribution by conserved glutamate residues to an ion‐selectivity site in the L‐type Ca2+ channel pore

• Published in: FEBS letters 1993-12, Vol.335 (2), p.265-269
• Main Authors: Mikala, Gabor, Bahinski, Anthony, Yatani, Atsuko, Tang, Shaoqing, Schwartz, Arnold
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Barium - metabolism; Binding Sites; Biological and medical sciences; Calcium channel; Calcium Channels - chemistry; Calcium Channels - metabolism; Cell membranes. Ionic channels. Membrane pores; Cell structures and functions; Conserved Sequence; Fundamental and applied biological sciences. Psychology; Glutamates - physiology; Glutamic Acid; Humans; Ion permeation; Molecular and cellular biology; Molecular Sequence Data; Mutation; Pore structure; Sequence Homology, Amino Acid; Site-directed mutagenesis; Sodium - metabolism; SS1-SS2 region; Structure-Activity Relationship
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(93)80743-E

In voltage‐gated cation channels, it is thought that residues responsible for ion‐selectivity are located within the pore‐lining SS1‐SS2 segments. In this study, we compared the ion permeation properties of mutant calcium channels in which highly conserved glutamate residues, located at analogous positions in the SS2 regions of all four motifs, were individually replaced. All of the mutants exhibited a loss of selectivity for divalent over monovalent cations. However, the permeation properties of the individual mutants varied in a position dependent manner. The results provide strong evidence that these glutamate residues, positioned at equivalent locations in the aligned sequences, play significantly different roles in forming the selectivity barrier of the calcium channel, and are probably arranged in an asymmetrical manner inside the ion‐conducting pore.