Selectivity filters and cysteine-rich extracellular loops in voltage-gated sodium, calcium, and NALCN channels.

ABSTRACT: How nature discriminates sodium from calcium ions in eukaryotic channels has been difficult to resolve because they contain four homologous, but markedly different repeat domains. We glean clues from analyzing the changing pore region in sodium, calcium and NALCN channels, from single-cell eukaryotes to mammals. Alternative splicing in invertebrate homologs provides insights into different structural features underlying calcium and sodium selectivity. NALCN generates alternative ion selectivity with splicing that changes the high field strength (HFS) site at the narrowest level of the hourglass shaped pore where the selectivity filter is located. Alternative splicing creates NALCN isoforms, in which the HFS site has a ring of glutamates contributed by all four repeat domains (EEEE), or thr

SUBMITTER: Stephens RF 

PROVIDER: S-EPMC4436565 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature