Regulation of the Voltage Gated K&lt;sup&gt;+&lt;/sup&gt; Channel K&lt;sub&gt;v1.3&lt;/sub&gt; by Recombinant Human Klotho Protein

Ahmad Almilaji; Sabina Honisch; Guilai Liu; Bernat Elvira; Sumant Singh Ajay; Zohreh Hosseinzadeh; Musaab Ahmed; Carlos Muñoz; Mentor Sopjani; Florian Lang

doi:10.1159/000368472

Abstract

Background/Aims: Klotho, a protein mainly produced in the kidney and released into circulating blood, contributes to the negative regulation of 1,25(OH)2D3 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+ channel Kv1.3. Methods: cRNA encoding Kv1.3 (KCNA3) was injected into Xenopus oocytes and depolarization induced outward current in Kv1.3 expressing Xenopus 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+ 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). Kv1.3 protein abundance in Jcam cells was determined utilising fluorescent antibodies in flow cytometry. Results: In Kv1.3 expressing Xenopus oocytes the Kv1.3 currents and the protein abundance of Kv1.3 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 Kv currents and Kv1.3 protein abundance in Jcam cells. Conclusion: Alpha Klotho protein enhances Kv1.3 channel abundance and Kv1.3 currents in the plasma membrane, an effect depending on its β-glucuronidase activity.

Keywords

KlothoInternal medicineEndocrinologyChemistryXenopusMolecular biologyKidneyBiologyBiochemistryMedicine

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Publication Info

Year: 2014
Type: article
Volume: 39
Issue: 6
Pages: 609-622
Citations: 5604
Access: Closed

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APA Style

                            
                                
                                    Ahmad Almilaji, 
                                
                                    Sabina Honisch, 
                                
                                    Guilai Liu
                                
                                et al.
                            
                            (2014). 
                            Regulation of the Voltage Gated K&lt;sup&gt;+&lt;/sup&gt; Channel K&lt;sub&gt;v1.3&lt;/sub&gt; by Recombinant Human Klotho Protein. 
                            Kidney & Blood Pressure Research
                            , 39
                            (6)
                            , 609-622.
                            https://doi.org/10.1159/000368472
                        

Identifiers

DOI: 10.1159/000368472

Regulation of the Voltage Gated K<sup>+</sup> Channel K<sub>v1.3</sub> by Recombinant Human Klotho Protein