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Research Papers

A mutually exclusive alternative exon of slo1 codes for a neuronal BK channel with altered function

Malle Soom, Guido Gessner, Heike Heuer, Toshinori Hoshi and Stefan H Heinemann

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Large-conductance Ca2+- and voltage-activated K+ (BK) channels are comprised of four pore-forming α-subunits (Slo1), whose mRNA is alternatively spliced in a cell-specific manner. Here we report the first case of a correctly spliced mutually exclusive exon in a mammalian (human and mouse) BK channel; an exon coding for the region from S6 to the RCK1 domain is exchanged for an alternative exon of the same length. The slo1 transcript with this novel exon is present in native brain tissues and inclusion of the alternative exon profoundly alters the channel's gating characteristics: faster activation at low Ca2+ concentrations and greater open probability at resting membrane potential at high Ca2+ concentrations. The novel gating features conferred by the alternative exon are dominant over those of the commonly described Slo1 variant when coexpressed. The evolutionarily-preserved splicing of the Slo1 S6-RCK1 linker segment possess great potential to fine-tune neuronal excitability.

Authors

Malle Soom

Friedrich Schiller University Jena

Guido Gessner

Friedrich Schiller University Jena

Heike Heuer

Fritz Lipmann Institute for Age Research

Toshinori Hoshi

University of Pennsylvania

Stefan H Heinemann

Friedrich Schiller University Jena

Purchase article for $19

Subscribe to this journal for $79/year