A mutually exclusive alternative exon of slo1 codes for a neuronal BK channel with altered function.
Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels are comprised of four pore-forming -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 Ca(2+) concentrations and greater open probability at resting membrane potential at high Ca(2+) 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.
Soom
Malle
M
Center for Molecular Biomedicine, Department of Biophysics, Friedrich Schiller University Jena, Jena, Germany.
Gessner
Guido
G
Heuer
Heike
H
Hoshi
Toshinori
T
Heinemann
Stefan H
SH
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D005091:Exons; D006801:Humans; D007700:Kinetics; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D014018:Tissue Distribution
C494841:KCNMA1 protein, human; C465449:Kcnma1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels