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This Article Full Text Full Text (PDF) Supplemental Data Supplemental data All Versions of this Article: 573/2/329    most recent jphysiol.2006.106922v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Korovkina, V. P. Articles by England, S. K. Search for Related Content PubMed PubMed Citation Articles by Korovkina, V. P. Articles by England, S. K. Related Collections Cellular

¹ Department of Physiology and Biophysics, Carver College of Medicine, University of Iowa, 6-432 BSB Iowa City, IA 52242, USA

Large conductance Ca²⁺- 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 Ca²⁺. 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 Ca²⁺ release from intracellular stores resulted in translocation of the C-termini of mK44 to the cell membrane and co-localization with its N-termini. 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 N-myristoylation site did not produce current when expressed alone, but formed a functional channel when co-expressed with the N-terminus. These findings provide novel insight into cell-specific regulation of maxi-K channel function.

(Received 3 February 2006; accepted after revision 2 March 2006; first published online 9 March 2006)
Corresponding author S. K. England: Department of Physiology and Biophysics, Carver College of Medicine, University of Iowa, 6-432 BSB Iowa City, IA 52242, USA. Email: sarah-england{at}uiowa.edu

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				E. G. Moczydlowski The maxi K+ channel of human myometrium reveals a split personality J. Physiol., June 1, 2006; 573(2): 286 - 286. [Full Text] [PDF]