Translocation of an endoproteolytically cleaved maxi-K channel isoform: mechanisms to induce human myometrial cell repolarization

The Journal of Physiology
Victoria P KorovkinaSarah K England

Abstract

Large conductance Ca(2+)- and voltage-activated K+ (maxi-K) channels modulate human myometrial smooth muscle cell (hMSMC) excitability; however, the role of individual alternatively spliced isoforms remains unclear. We have previously shown that the transcript of a human maxi-K channel isoform (mK44) is expressed predominantly in myometrial and aortic smooth muscle and forms a functional channel in heterologous expression systems. The mK44 isoform contains unique consensus motifs for both endoproteolytic cleavage and N-myristoylation, although the function of these post-translational modifications is unknown. The goal of these studies was to determine the role of post-translational modifications in regulating mK44 channel function in hMSMCs. An mK44-specific antibody indicated that this channel is localized intracellularly in hMSMCs and translocates to the cell membrane in response to increases in intracellular Ca(2+). Immunological analyses using an N-terminally myc-tagged mK44 construct demonstrated endoproteolytical cleavage of mK44 in hMSMCs resulting in membrane localization of the mK44 N-termini and intracellular retention of the pore-forming C-termini. Caffeine-induced Ca(2+) release from intracellular stores resulted in...Continue Reading

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Citations

Jun 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Abderrahmane AliouaLigia Toro
Jan 2, 2009·American Journal of Physiology. Cell Physiology·Victoria P KorovkinaSarah K England
Aug 5, 2010·American Journal of Physiology. Endocrinology and Metabolism·Stephanie L Pierce, Sarah K England
Jun 29, 2007·Seminars in Cell & Developmental Biology·Adam M BrainardSarah K England
Feb 3, 2011·American Journal of Obstetrics and Gynecology·Pooja MittalSonia S Hassan
Aug 19, 2014·Frontiers in Physiology·Ramón A LorcaSarah K England
Jan 20, 2005·Gene·Stefan StammHermona Soreq
Mar 18, 2006·The Journal of Physiology·Edward G Moczydlowski
Jul 31, 2013·Journal of Perinatal Medicine·Piya ChaemsaithongTinnakorn Chaiworapongsa
Dec 19, 2020·Acta Physiologica·Manasi MalikSarah K England

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