Referenced in: none

Automatically associated channels: TREK1 , TREK2

Title: The isoforms generated by alternative translation initiation adopt similar conformation in the selectivity filter in TREK-2.

Authors: Ren-Gong Zhuo, Peng Peng, Xiao-Yan Liu, Shu-Zhuo Zhang, Jiang-ping Xu, Jian-quan Zheng, Xiao-Li Wei, Xiao-Yun Ma

Journal, date & volume: J. Physiol. Biochem., 2015 Aug 14 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26271386

Abstract
TREK-2 (TWIK-related K(+) channel-2), a member of two-pore domain potassium (K2P) channel family, tunes cellular excitability via conducting leak or background currents. In TREK-2, the isoforms generated by alternative translation initiation (ATI) mechanism exhibit large divergence in unitary conductance, but similar in selectivity to K(+). Up to now, the structural basis for this similarity in ion selectivity is unknown. Here, we report that externally applied Ba(2+) inhibits the currents of TREK-2 in a concentration- and time-dependent manner. The blocking effect is blunted by elevated extracellular K(+) or mutation of S4 K(+) binding site, which suggests that the inhibitory mechanism of Ba(2+) is due to its competitive docking properties within the selectivity filter (SF). Next, we demonstrate that all the ATI isoforms exhibit analogous behaviors upon the application of Ba(2+) and alteration of extracellular pH (pHo), which acts on the outer position of the SF. These results strongly support the notion that all the ATI isoforms of TREK-2 possess resembled SF conformation in S4 site and the position defined by pHo, which implicates that neither the role of N-terminus (Nt) nor the unitary conductance is associated with SF conformation. Our findings might help to understand the detail gating mechanism of TREK-2 and K2P channels.