Kidney & Blood Pressure Research· 2014Q2
Regulation of the Voltage Gated K<sup>+</sup> Channel K<sub>v1.3</sub> by Recombinant Human Klotho Protein
- 5,609citations
- Q2SCImago
- 2014year
Short summary
Recombinant human Klotho protein significantly enhances Kv1.3 channel abundance and currents in cell membranes, an effect dependent on Klotho's beta-glucuronidase activity.
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Key points
- Recombinant human Klotho protein increased Kv1.3 channel currents and protein abundance in Xenopus oocytes.
- Similar increases in Kv1.3 currents and protein were observed in Jcam lymphoma cells.
- The enhancing effect of Klotho on Kv1.3 was reversed by a beta-glucuronidase inhibitor (DSAL).
- Klotho's beta-glucuronidase activity is essential for its regulation of Kv1.3 channel abundance.
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Abstract
<b><i>Background/Aims: </i></b>Klotho, a protein mainly produced in the kidney and released into circulating blood, contributes to the negative regulation of 1,25(OH)<sub>2</sub>D<sub>3</sub> formation and is thus a powerful regulator of mineral metabolism. As β-glucuronidase, alpha Klotho protein further regulates the stability of several carriers and channels in the plasma membrane and thus regulates channel and transporter activity. Accordingly, alpha Klotho protein participates in the regulation of diverse functions seemingly unrelated to mineral metabolism including lymphocyte function. The present study explored the impact of alpha Klotho protein on the voltage gated K<sup>+</sup> channel K<sub>v1.3</sub>. <b><i>Methods: </i></b>cRNA encoding K<sub>v1.3</sub> (KCNA3) was injected into <i>Xenopus</i> oocytes and depolarization induced outward current in K<sub>v1.3</sub> expressing <i>Xenopus</i> oocytes determined utilizing dual electrode voltage clamp. Experiments were performed without or with prior treatment with recombinant human Klotho protein (50 ng/ml, 24 hours) in the absence or presence of a β-glucuronidase inhibitor D-saccharic acid-1,4-lactone (DSAL, 10 µM). Moreover, the voltage gated K<sup>+</sup> current was determined in Jcam lymphoma cells by whole cell patch clamp following 24 hours incubation without or with recombinant human Klotho protein (50 ng/ml, 24 hours). K<sub>v1.3</sub> protein abundance in Jcam cells was determined utilising fluorescent antibodies in flow cytometry. <b><i>Results: </i></b>In K<sub>v1.3</sub> expressing <i>Xenopus</i> oocytes the K<sub>v1.3</sub> currents and the protein abundance of K<sub>v1.3</sub> were both significantly enhanced after treatment with recombinant human Klotho protein (50 ng/ml, 24 hours), an effect reversed by presence of DSAL. Moreover, treatment with recombinant human Klotho protein increased K<sub>v</sub> currents and K<sub>v1.3</sub> protein abundance in Jcam cells. <b><i>Conclusion: </i></b>Alpha Klotho protein enhances K<sub>v1.3</sub> channel abundance and K<sub>v1.3</sub> currents in the plasma membrane, an effect depending on its β-glucuronidase activity.
The authors' abstract, as published at the source. Kidney & Blood Pressure Research, 2014 · DOI ↗
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Field: Nephrology
NephrologyMedicine