Expression of Ca2+‐activated BK channel mRNA and its splice variants in the rat cochlea

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Abstract
Voltage‐activated K+ channels are important for shaping the receptor potentials of cochlear hair cells. In particular, the functional maturation of inner hair cells in mice around the onset of hearing coincides with the expression of a large, fast K+ conductance, probably mediated by Ca2+‐activated K+ (BK) channels. In hearing organs of lower vertebrates, frequency tuning depends on BK‐type K+ channels with different kinetics. Kinetics are varied by alternative splicing of the channels' α subunits and combination with modulating β subunits. It is unclear whether similar mechanisms “fine tune” mammalian hair cells. We used various polymerase chain reaction (PCR) approaches to screen rat cochleae for splice variants of BK‐type α subunits. We isolated mainly minimal variants and only occasionally splice variants with additional inserts. We conclude that α subunits with different kinetics are not substantially used in the rat cochlea. However, we isolated six variants differing in their extreme C‐terminal sequences, which may be involved in the targeting of the channel protein. By using reverse transcriptase‐PCR, we demonstrated also the expression of transcripts for several β subunits. In situ hybridization experiments revealed strict coexpression of α with β1 transcripts. In inner hair cells, strong labeling emerged shortly before the onset of hearing. Labeling of outer hair cells appeared later and generally weaker. Thus, our molecular data confirm electrophysiological results that suggested that BK channels underlie the large K+ conductance in inner hair cells of mammals. Extensive splicing of BK channel transcripts, however, does not seem to be used in mammalian hair cells as is done in lower vertebrates. J. Comp. Neurol. 455:198–209, 2003.
Funding Information
  • German research council (DFG) (Ru 442/3)