Evidence map›Paper›PMID 19701239›Full record

ArticleActa pharmacologica Sinica2009

Functional study of the effect of phosphatase inhibitors on KCNQ4 channels expressed in Xenopus oocytes.

Tzu-rong Su, Cay-huyen Chen, Shih-jen Huang, Chun-yi Lee, Mao-chang Su, Gwan-hong Chen, Shuan-yow Li, Jiann-jou Yang, Min-jon Lin

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Article in Acta pharmacologica Sinica, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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3citing papers in PubMed
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3 · Its place in the literature

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3 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Tzu-rong SuAntai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Tong-Kang, Pintong, Taiwan, China.
Cay-huyen Chen
Shih-jen Huang
Chun-yi Lee
Mao-chang Su
Gwan-hong Chen
Shuan-yow Li
Jiann-jou Yang
Min-jon Lin

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimKCNQ4 channels play an important part in adjusting the function of cochlear outer hair cells. The aim of this study was to investigate the effects of ser/thr phosphatase inhibitors on human KCNQ4 channels expressed in Xenopuslaevis oocytes.

methodsSynthetic cRNA encoding human KCNQ4 channels was injected into Xenopus oocytes. We used a two-electrode voltage clamp to measure the ion currents in the oocytes.

resultsWild-type KCNQ4 expressed in Xenopus oocytes showed the typical properties of slow activation kinetics and low threshold activation. The outward K(+) current was almost completely blocked by a KCNQ4 blocker, linopirdine (0.25 mmol/L). BIMI (a PKC inhibitor) prevented the effects of PMA (a PKC activator) on the KCNQ4 current, indicating that PKC may be involved in the regulation of KCNQ4 expressed in the Xenopus oocyte system. Treatment with the ser/thr phosphatase inhibitors, cyclosporine (2 micromol/L), calyculin A (2 micromol/L) or okadaic acid (1 micromol/L), caused a significant positive shift in V(1/2) and a decrease in the conductance of KCNQ4 channels. The V(1/2) was shifted from -14.6+/-0.5 to -6.4+/-0.4 mV by cyclosporine, -18.8+/-0.5 to -9.2+/-0.4 mV by calyculin A, and -14.1+/-0.5 to -0.7+/-0.6 mV by okadaic acid. Moreover, the effects of these phosphatase inhibitors (okadaic acid or calyculin A) on the induction of a positive shift of V(1/2) were augmented by further addition of PMA.

conclusionThese results indicate that ser/thr phosphatase inhibitors can induce a shift to more positive potentials of the activation curve of the KCNQ4 current. It is highly likely that the phosphatase functions to balance the phosphorylated state of substrate protein and thus has an important role in the regulation of human KCNQ4 channels expressed in Xenopus oocytes.

Indexed as

Action PotentialsAnimalsCyclosporineHumansIndolesKCNQ Potassium ChannelsMaleimidesMarine ToxinsOkadaic AcidOocytesOxazolesPhosphoprotein PhosphatasesPhosphoric Monoester HydrolasesPotassium Channel BlockersProtein Kinase CPyridinesbisindolylmaleimide Icalyculin ACyclosporineIndolesKCNQ4 protein, humanKCNQ Potassium ChannelslinopirdineMaleimidesMarine ToxinsOkadaic AcidOxazolesPhosphoprotein PhosphatasesPhosphoric Monoester HydrolasesPotassium Channel BlockersProtein Kinase CPyridines

Identifiers

PMID19701239
PMCPMC4007189

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.