The functional role of alternative splicing of Ca(2+)-activated K+ channels in auditory hair cells.
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.
Department of Physiology, University of Wisconsin Medical School, Madison 53706, USA.
E M
EM
Jones
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Gray-Keller
J J
JJ
Art
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Fettiplace
D017398:Alternative Splicing; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002417:Cattle; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000235:genetics; D006198:Hair Cells, Auditory / Q000378:metabolism*; D007700:Kinetics; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics*; D024681:Potassium Channels, Calcium-Activated; D018075:RNA, Complementary / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014426:Turtles; D014982:Xenopus laevis
D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D018075:RNA, Complementary; D002118:Calcium