Dual regulation of renal Kir7.1 potassium channels by protein Kinase A and protein Kinase C

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• 作者：Wei Zhang ; Edgar Zitron ; Ramona Bloehs ; S ; ra Mü ; ller-Krebs ; Eberhard Scholz ; Martin Zeier ; Hugo Katus ; Christoph Karle ; Vedat Schwenger
• 关键词：Electrophysiology ; Potassium channel ; Kir7.1 ; Signal transduction ; Renal potassium secretion ; Protein kinase A ; Protein kinase C ; Xenopus oocyte expression system
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2008
• 出版时间：19 December 2008
• 年：2008
• 卷：377
• 期：3
• 页码：981-986
• 全文大小：836 K

文摘

The renal inward rectifier potassium channel Kir7.1 has been proposed to be functionally important for tubular K⁺ recycling and secretion. This study investigated the regulation of Kir7.1 by PKA and PKC.

Cloned human Kir7.1 channels were expressed heterologously in Xenopus oocytes. After pharmacological PKC activation, Kir7.1 currents were strongly inhibited. Co-application of PKC inhibitors attenuated this effect. Inactivation of PKC consensus sites also strongly attenuated the effect with a single site (²⁰¹S) being essential for almost the total PKC sensitivity. In contrast, PKA activation induced an increase of Kir7.1 currents. This effect was absent in mutant Kir7.1 channels lacking PKA consensus site ²⁸⁷S.

In summary, this study demonstrates the dual regulation of Kir7.1 channel function by PKA and PKC. Structurally, these regulations depend on two key residues in the C-terminal channel domain (^Ser201 for PKC and ^Ser287 for PKA).