HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 296/3/C433    most recent 00357.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) 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.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Nardilysin convertase regulates the function of the maxi-K channel isoform mK44 in human myometrium

Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa

Submitted 10 July 2008 ; accepted in final form 29 December 2008

In smooth muscle, large-conductance Ca²⁺- and voltage-activated K⁺ channels from the gene KCNMA (maxi-K channels) generate isoforms with disparate responses to contractile stimuli. We previously showed that the human myometrium expresses high levels of the splice variant of the maxi-K channel containing a 44-amino acid insertion (mK44). The studies presented here demonstrate that nardilysin convertase, a Zn²⁺-dependent metalloprotease of the insulinase family, regulates the plasma membrane expression of mK44 and its response to increases in intracellular Ca²⁺. We show that nardilysin convertase isoform 1 is present in human myometrium and colocalizes with mK44. Studies indicate that nardilysin convertase regulates 1) retention of the mK44 COOH-terminal fragment in the endoplasmic reticulum in quiescent myometrial smooth muscle and 2) Ca²⁺-induced translocation of mK44 to the plasma membrane. In mouse fibroblasts, nardilysin convertase significantly attenuates mK44-dependent current. In human myometrial smooth muscle cells, inhibition of nardilysin convertase promotes membrane localization of mK44 and an increase in maxi-K current. Overall, our data indicate that, in human myometrium, nardilysin convertase and mK44 channels are a part of the molecular mechanism that regulates the excitability of smooth muscle cells.

N-arginine dibasic convertase; smooth muscle; large-conductance calcium-activated potassium channel