Interacting effects of N-terminal variation and strex exon splicing on slo potassium channel regulation by calcium,phosphorylation, and oxidation |
| |
Authors: | Erxleben Christian Everhart Angela L Romeo Charles Florance Hannah Bauer Mary Beth Alcorta David A Rossie Sandra Shipston Michael J Armstrong David L |
| |
Institution: | Laboratory of Signal Transduction, NIEHS, National Institutes of Health, 111 Alexander Drive, Research Triangle Park, NC 27709, USA. |
| |
Abstract: | We have investigated the structural basis for the phenotype of a native rat Slo (rSlo) potassium channel (BK(Ca); KCNMA1) in a rat pituitary cell line, GH(4)C(1). Opposing regulation of these calcium- and voltage-activated potassium channels by cAMP- and cGMP-dependent protein kinases requires an alternatively spliced exon (strex) of 59 amino acids in the cytoplasmic C terminus of the pore-forming alpha subunit encoded by rslo. However, inclusion of this cysteine-rich exon produces a 10-fold increase in the sensitivity of the channels to inhibition by oxidation. Inclusion of the strex exon also increases channel sensitivity to stimulation by calcium, but responses in the physiological ranges of calcium and voltage require coassembly with beta(1) subunits. With strex present, however, beta(1) subunits only stimulated channels assembled from rSlo alpha subunits with a truncated N terminus beginning MDALI-. Thus N-terminal variation and strex exon splicing in rSlo interact to produce BK(Ca) channels with a physiologically relevant phenotype. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|