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The Functional Role of Alternative Splicing of Ca 2+ ‐Activated K + Channels in Auditory Hair Cells
Author(s) -
JONES E.M. C.,
GRAYKELLER M.,
ART J. J.,
FETTIPLACE R.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb11299.x
Subject(s) - bk channel , calcium activated potassium channel , patch clamp , xenopus , hair cell , r type calcium channel , protein subunit , chemistry , calcium channel , alternative splicing , microbiology and biotechnology , t type calcium channel , gene isoform , biophysics , g alpha subunit , beta (programming language) , potassium channel , voltage dependent calcium channel , biology , calcium , inner ear , biochemistry , neuroscience , receptor , gene , organic chemistry , computer science , programming language
Turtle auditory hair cells are frequency tuned by the activity of large‐conductance calcium‐activated potassium (KCa) channels, the frequency range being dictated primarily by the channel kinetics. Seven alternatively spliced isoforms of the KCa channel alpha‐subunit, resulting from exon insertion at two splice sites, were isolated from turtle hair cells. These, when expressed in Xenopus oocytes, produced KCa channels with a range of apparent calcium sensitivities and channel kinetics. However, most expressed channels were less calcium sensitive than the hair cells' native KCa channels. Coexpression of alpha‐subunit with a bovine beta‐subunit substantially increased the channel's calcium sensitivity while markedly slowing its kinetics, but kinetic differences between isoforms were preserved. These data suggest a molecular mechanism for hair cell frequency tuning involving differential expression of different KCa channel alpha‐subunits in conjunction with an expression gradient of a regulatory beta‐subunit.