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

Channels
Malle SoomStefan H Heinemann

Abstract

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.

Citations

Feb 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Guido GessnerStefan H Heinemann
Feb 7, 2009·Physiology·Shangwei HouToshinori Hoshi
Sep 20, 2011·Expert Opinion on Therapeutic Targets·Prosper N'Gouemo
Feb 6, 2015·Proceedings of the National Academy of Sciences of the United States of America·Timothy I WebbMark A Hollywood
Jul 30, 2011·Journal of Neuroscience Research·Yoshihisa SakaiBernd Sokolowski
Jan 31, 2014·Channels·Trey S RottgenGregory M Dick
Feb 21, 2016·Pharmacology & Therapeutics·Susumu OhyaKatsuhiko Muraki
Feb 12, 2019·Annual Review of Physiology·Vivian Gonzalez-Perez, Christopher J Lingle
Apr 11, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yutao TianToshinori Hoshi
Dec 15, 2015·American Journal of Physiology. Cell Physiology·K I HanniganK D Thornbury
Jun 19, 2019·Nature Communications·Melina MathurChristina D Smolke
Mar 7, 2017·Nature·Nicholas W BellonoDavid Julius
Mar 3, 2021·PLoS Computational Biology·Su Datt LamChristine A Orengo

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