{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T17:49:20Z","timestamp":1757699360353},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T00:00:00Z","timestamp":1149033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p>Large conductance Ca<jats:sup>2+<\/jats:sup>\u2010 and voltage\u2010activated K+ (maxi\u2010K) 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\u2010K 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 <jats:italic>N<\/jats:italic>\u2010myristoylation, although the function of these post\u2010translational modifications is unknown. The goal of these studies was to determine the role of post\u2010translational modifications in regulating mK44 channel function in hMSMCs. An mK44\u2010specific antibody indicated that this channel is localized intracellularly in hMSMCs and translocates to the cell membrane in response to increases in intracellular Ca<jats:sup>2+<\/jats:sup>. Immunological analyses using an N\u2010terminally myc\u2010tagged mK44 construct demonstrated endoproteolytical cleavage of mK44 in hMSMCs resulting in membrane localization of the mK44 N\u2010termini and intracellular retention of the pore\u2010forming C\u2010termini. Caffeine\u2010induced Ca<jats:sup>2+<\/jats:sup> release from intracellular stores resulted in translocation of the C\u2010termini of mK44 to the cell membrane and co\u2010localization with its N\u2010termini. Translocation of mK44 channels to the cell membrane was concomitant with repolarization of the hMSMCs. Endoproteolytic digest of mK44 did not occur in HEK293 cells or mouse fibroblasts. MK44 truncated at a putative <jats:italic>N<\/jats:italic>\u2010myristoylation site did not produce current when expressed alone, but formed a functional channel when co\u2010expressed with the N\u2010terminus. These findings provide novel insight into cell\u2010specific regulation of maxi\u2010K channel function.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.106922","type":"journal-article","created":{"date-parts":[[2006,3,10]],"date-time":"2006-03-10T01:32:57Z","timestamp":1141954377000},"page":"329-341","source":"Crossref","is-referenced-by-count":20,"title":["Translocation of an endoproteolytically cleaved maxi\u2010K channel isoform: mechanisms to induce human myometrial cell repolarization"],"prefix":"10.1113","volume":"573","author":[{"given":"Victoria P.","family":"Korovkina","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam M.","family":"Brainard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah 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