Up-regulation of the Inwardly Rectifying K⁺ Channel Kir2.1 (KCNJ2) by Protein Kinase B (PKB/Akt) and PIKfyve

Overview

Journal J Membr Biol

Date 2012 Nov 29

PMID 23188060

Citations 14

Authors

Carlos Munoz

Ahmad Almilaji

Iwan Setiawan

Michael Foller

Florian Lang

Affiliations

Soon will be listed here.

Abstract

The inward rectifier K⁺ channel Kir2.1 contributes to the maintenance of the resting cell membrane potential in excitable cells. Loss of function mutations of KCNJ2 encoding Kir2.1 result in Andersen-Tawil syndrome, a disorder characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features. The ubiquitously expressed protein kinase B (PKB/Akt) activates the phosphatidylinositol-3-phosphate-5-kinase PIKfyve, which in turn regulates a variety of carriers and channels. The present study explored whether PKB/PIKfve contributes to the regulation of Kir2.1. To this end, cRNA encoding Kir2.1 was injected into Xenopus oocytes with and without additional injection of cRNA encoding wild type PKB (PKB), constitutively active (T308D,S473D)PKB or inactive (T308A,S473A)PKB. Kir2.1 activity was determined by two-electrode voltage-clamp. As a result, PKB and (T308D,S473D)PKB, but not (T308A,S473A)PKB, significantly increased Kir2.1-mediated currents. The effect of PKB was mimicked by coexpression of PIKfyve but not of (S318A)Pikfyve lacking the PKB phosphorylation site. The decay of Kir2.1-mediated currents after inhibition of channel insertion into the cell membrane by brefeldin A (5 μM) was similar in oocytes expressing Kir2.1 + PKB or Kir2.1 + PIKfyve to those expressing Kir2.1 alone, suggesting that PKB and PIKfyve influence channel insertion into rather than channel retrieval from the cell membrane. In conclusion, PKB and PIKfyve are novel regulators of Kir2.1.

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