Molecular analyses of KCNQ1-5 potassium channel mRNAs in rat and guinea pig inner ears:: expression, cloning, and alternative splicing

Conclusion. Expression of neuronal Kcnq gene family transcripts in the inner ear provides further evidence for cochlear M-type currents and for complex molecular heterogeneities of voltage-gated potassium channels composed of various KCNQ subunits and/or alternative splice variants. Furthermore, important roles in regulation of cellular excitability in the auditory system, and hearing disorders related to (hyper) excitability, e. g. tinnitus, are implied. Background. Voltage-gated potassium channels play key roles in hearing, as evidenced by deafness resulting from disruption of genes encoding, for example, KCNQ1 or KCNQ4 subunits. Other members of the Kcnq gene family (Kcnq2, 3, and 5) are the molecular correlates of M currents, which regulate neuronal excitability. The expression of the latter has not previously been thoroughly investigated in the inner ear. Objective. The aim of this study was to identify genetic correlates of M currents, previously identified in cochlear hair cells by electrophysiological methods. Materials and methods. Expression of Kcnq genes was investigated by reverse transcription-polymerase chain reaction (RT-PCR) using subtype-specific primers with total RNA isolated from whole guinea pig or rat cochlea as template. PCR products were confirmed by direct DNA sequencing. Results. All members of the Kcnq family were expressed in guinea pig and rat cochlea. Cochlear expression of Kcnq2 exhibited two alternatively spliced forms, lacking exons 8, 15a, and 8, 12a, 15a, respectively. Novel molecular sequence data, e. g. guinea pig Kcnq cDNA sequences, were deposited in GenBank (AY684985-AY684990).