IndraLab

"The mechanism by which PIP mediates VSD-pore coupling in KCNQ1 remains to be understood."

"The role of PIP 2 modulation of native cardiac KCNQ1 channels is less well established."

"The above results suggest that while CP1 acts similarly to PIP in that it mediates VSD-pore coupling in KCNQ1 channels, its function may differ from that of PIP , which does not affect VSD activation or opens the pore without VSD activation ."

"In this configuration, hERG and KCNQ1 biophysical changes induced by PIP 2 insertion are quite similar (slowed deactivation with no effect on activation)."

"Similar to K channels, application of PIP to the KCNQ1 and hERG channels slows channel run-down.58, 59 For KCNQ1, three binding sites have been proposed; one on the VSD, one on the linker between the VSD and pore domain, and one directly adjacent to the pore.55, 56, 57 The multiple binding sites therefore means that modulation of KCNQ1 by PIP is complex.PIP is absolutely necessary to bridge the intramolecular interactions between the S4 helix of the VSD domain,60 this therefore enhances the VSD coupling to the pore.53, 61 PIP also appears to induce a large scale conformational change of the intracellular domain of the channel, which is also important for channel gating."

"This idea is further supported by the recent discovery of a PIP 2 -mimetic compound, which enhances KCNQ1 VSD-pore coupling through occupancy of this second site."

"KCNQ1 and KCNE1, KCNQ4, and KCNQ5 channels are also reactivated by PIP 2 after inhibition by polylysine, showing that all KCNQ family members are PIP 2 sensitive."

"The results indicate that PIP (2) indirectly activates hepatocellular KCNQ1 like channels via cytoskeletal rearrangement involving PKC activation."

"Here we show that the auxiliary subunit of I (Ks), KCNE1, increases PIP (2) sensitivity 100-fold over channels formed by the pore forming KCNQ1 subunits alone, which effectively amplifies current because native PIP (2) levels in the membrane are insufficient to activate all KCNQ1 channels."

"We found that CP1 could substitute for PIP to recover KCNQ1 currents that were abolished by depletion of membrane PIP ."