Dataset Information

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

ABSTRACT: In smooth muscle, large-conductance Ca(2+)- 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 Zn(2+)-dependent metalloprotease of the insulinase family, regulates the plasma membrane expression of mK44 and its response to increases in intracellular Ca(2+). 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) Ca(2+)-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.

SUBMITTER: Korovkina VP

PROVIDER: S-EPMC2660261 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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

Korovkina Victoria P VP Stamnes Susan J SJ Brainard Adam M AM England Sarah K SK

American journal of physiology. Cell physiology 20081231 3

In smooth muscle, large-conductance Ca(2+)- 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 Zn(2+)-dependent metalloprotease of the insulinase family, regulates the plasma membrane ...[more]

PMID: 19118164

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Dataset Information

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

Publications

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

Similar Datasets

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