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The role of Ca2+-activated K+ channel spliced variants in the tonotopic organization of the turtle cochlea

By E M C Jones, M Gray-Keller and R Fettiplace

Abstract

Turtle auditory hair cells contain multiple isoforms of the pore-forming α-subunit of the large-conductance Ca2+-activated K+ (KCa) channel due to alternative splicing at two sites. Six splice variants were studied by expression in Xenopus oocytes.The isoforms possessed differences in apparent Ca2+ sensitivity and kinetics. The lowest Ca2+ sensitivity was observed in a novel variant resulting from a 26 amino acid deletion around one of the splice sites.Co-expression of a bovine β-subunit slowed the current relaxation 10-fold compared with channels formed from α-subunits alone but preserved the original order of kinetic differences. The β-subunit also increased the Ca2+ sensitivity of isoforms to bring them nearer the range of sensitivity of the native KCa channels of the hair cell.With channels formed from α-subunits or α+β-subunits, the half-activation voltage in a fixed Ca2+ concentration, and the time constant of the current relaxation, varied linearly with the combined size of the insertions/deletions at the splice sites.Experiments in which the β/α concentration ratio was varied indicated that the β-subunit exerts an all-or-none effect on the Ca2+ sensitivity and kinetics of the channel.Co-expression of an avian β2-subunit had effects on kinetics and Ca2+ sensitivity of several α-isoforms which were qualitatively similar to those produced by the bovine β-subunit.We conclude that differential expression of alternatively spliced α-subunit variants and a non-uniform distribution of a β-subunit can produce a range of KCa channel properties needed to explain the tonotopic organization of the turtle cochlea

Topics: Original Articles
Publisher: Blackwell Science Inc
OAI identifier: oai:pubmedcentral.nih.gov:2269449
Provided by: PubMed Central
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