The LQLP calcineurin docking site is a major determinant of the calcium-dependent activation of human TRESK background K+ channel.

ABSTRACT: Calcium-dependent activation of human TRESK (TWIK-related spinal cord K(+) channel, K2P18.1) depends on direct targeting of calcineurin to the PQIIIS motif. In the present study we demonstrate that TRESK also contains another functionally relevant docking site for the phosphatase, the LQLP amino acid sequence. Combined mutations of the PQIIIS and LQLP motifs were required to eliminate the calcium-dependent regulation of the channel. In contrast to the alanine substitutions of PQIIIS, the mutation of LQLP to AQAP alone did not significantly change the amplitude of TRESK activation evoked by the substantial elevation of cytoplasmic calcium concentration. However, the AQAP mutation slowed down the response to high calcium. In addition, modest elevation of [Ca(2+)], which effectively regulated

SUBMITTER: Czirjak G 

PROVIDER: S-EPMC4207969 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature