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

摘要

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 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. These data show that evolutionary preserved regulation of alternative Slo1 splicing of the S6-RCK1 linker creates fine-tuning of neuronal excitability.