Quasi-specific access of the potassium channel inactivation gate

Abstract

Many voltage-gated potassium channels open in response to membrane depolarization and then inactivate within milliseconds. Neurons use these channels to tune their excitability. In Shaker K+ channels, inactivation is caused by the cytoplasmic amino terminus, termed the inactivation gate. Despite having four such gates, inactivation is caused by the movement of a single gate into a position that occludes ion permeation. The pathway that this single inactivation gate takes into its inactivating position remains unknown. Here we show that a single gate threads through the intracellular entryway of its own subunit, but the tip of the gate has sufficient freedom to interact with all four subunits deep in the pore, and does so with equal probability. This pathway demonstrates that flexibility afforded by the inactivation peptide segment at the tip of the N-terminus is used to mediate function.

Demonstration of ion channel synthesis by isolated squid giant axon provides functional evidence for localized axonal membrane protein translation

“…Interestingly, we found that the recovery from inactivation kinetics for the new channels, resembled the potassium channels containing less than four identical Shaker channel subunits 54 , 55 , 69 . We have presented evidence that the Shaker channel subunits heterotetramerize with the squid K V channel subunits in Xenopus oocytes (Fig.…”

A niobium and tantalum co-doped perovskite cathode for solid oxide fuel cells operating below 500 °C

“…However, the electrode resistance of the GDC cell is only slightly lower than that of the SDC-based cell, being 0.056, 0.116 and 0.242 Ω cm 2 at these respective temperatures. Taking into consideration the ease and low-cost of the ceramic fabrication processes involved in the necessary scale-up5, GDC electrolyte fuel cells can be fabricated to a thickness of approximately 10–14 μm, though further reduction in GDC thickness is expected to boost the single cell performance by lowering its ohmic resistance69. Overall, the performance of the SCNT-based fuel cell surpasses the target of 500 mW cm −2 for SOFCs44, suggesting the possibility of practical operation even below 450 °C.…”

“…However, the low operating temperature (450-600 °C) typically leads to sluggish kinetics of the oxygen reduction reaction (ORR) at the cathode, with this being a major limitation to LT-SOFC performance456789.…”

“…Intensive research has been carried out in an effort to explore cathode compositions suitable for operation at low temperature467101112131415. Oxides offering high mixed ionic and electronic conductivities (MIECs) are considered to be some of the most promising candidates for the next generation of SOFC cathodes due to their extended active sites for ORR when compared with purely electronic conducting materials1617.…”

Single-particle cryo-EM structure of a voltage-activated potassium channel in lipid nanodiscs

“…In the Shaker Kv channel, for example, opening of the channel in response to membrane depolarization is only transient because the channel rapidly (msec) enters the N-type inactivated state ( Timpe et al, 1988 ; Zagotta et al, 1990 ). N-type inactivation occurs through a ball-and-chain mechanism wherein the amino-terminal region of the channel plugs the internal pore once it opens in response to membrane depolarization ( Demo and Yellen, 1991 ; Hoshi et al, 1990 ; Venkataraman et al, 2014 ; Zagotta et al, 1990 ; Zhou et al, 2001a2001 ). However, Shaker channels lacking this N-terminal region can still inactivate on a slower timescale (sec) through a process termed slow or C-type inactivation ( Hoshi et al, 1991 ).…”