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166) Taken together, these data suggest that in the absence of SURx, inverted channels can be formed from truncated Kir6.x subunits that are functionally active which may provide a new model for testing pharmacological modulators of Kir6.x, but also indicates the need for added caution when using truncated Kir6.2 mutants.
* Expression of truncated Kir6.2 promotes insertion of functionally inverted ATP-sensitive K+ channels.
- ATP-sensitive K+ (KATP) channels couple cellular metabolism to electrical activity in many cell types. Wild-type KATP channels are comprised of four pore forming (Kir6.x) and four regulatory (sulfonylurea receptor, SURx) subunits that each contain RKR endoplasmic reticulum retention sequences that serve to properly translocate the channel to the plasma membrane. Truncated Kir6.x variants lacking RKR sequences facilitate plasma membrane expression of functional Kir6.x in the absence of SURx; however, the effects of channel truncation on plasma membrane orientation have not been explored. To investigate the role of truncation on plasma membrane orientation of ATP sensitive K+ channels, three truncated variants of Kir6.2 were used (Kir6.2ΔC26, 6xHis-Kir6.2ΔC26, and 6xHis-EGFP-Kir6.2ΔC26). Oocyte expression of Kir6.2ΔC26 shows the presence of a population of inverted inserted channels in the plasma membrane, which is not present when co-expressed with SUR1. Immunocytochemical staining of intact and permeabilized HEK293 cells revealed that the N-terminus of 6xHis-Kir6.2ΔC26 was accessible on both sides of the plasma membrane at roughly equivalent ratios, whereas the N-terminus of 6xHis-EGFP-Kir6.2Δ26 was only accessible on the intracellular face. In HEK293 cells, whole-cell electrophysiological recordings showed a ca. 50% reduction in K+ current upon addition of ATP to the extracellular solution for 6xHis-Kir6.2ΔC26, though sensitivity to extracellular ATP was not observed in 6xHis-EGFP-Kir6.2ΔC26. Importantly, the population of channels that is inverted exhibited similar function to properly inserted channels within the plasma membrane. Taken together, these data suggest that in the absence of SURx, inverted channels can be formed from truncated Kir6.x subunits that are functionally active which may provide a new model for testing pharmacological modulators of Kir6.x, but also indicates the need for added caution when using truncated Kir6.2 mutants.
=>新発見の, 新しい, 現代的な, 新参の
Overview of adj new
The adj new has 11 senses (first 5 from tagged texts)
1. (310) new -- (not of long duration; having just (or relatively recently) come into being or been
made or acquired or discovered; "a new law"; "new cars"; "a new comet"; "a new friend"; "a new
year"; "the New World")
2. (36) fresh, new, novel -- (original and of a kind not seen before; "the computer produced a
completely novel proof of a well-known theorem")
3. (11) raw, new -- (lacking training or experience; "the new men were eager to fight"; "raw
recruits")
4. (5) new, unexampled -- (having no previous example or precedent or parallel; "a time of
unexampled prosperity")
5. (3) new -- (other than the former one(s); different; "they now have a new leaders"; "my new car
is four years old but has only 15,000 miles on it"; "ready to take a new direction")
6. new -- (unaffected by use or exposure; "it looks like new")
7. newfangled, new -- ((of a new kind or fashion) gratuitously new; "newfangled ideas"; "she buys
all these new-fangled machines and never uses them")
8. New -- (in use after medieval times; "New Eqyptian was the language of the 18th to 21st
dynasties")
9. Modern, New -- (used of a living language; being the current stage in its development; "Modern
English"; "New Hebrew is Israeli Hebrew")
10. new, young -- ((of crops) harvested at an early stage of development; before complete maturity;
"new potatoes"; "young corn")
11. new -- (unfamiliar; "new experiences"; "experiences new to him"; "errors of someone new to the
job")
Overview of adv new
The adv new has 1 sense (first 1 from tagged texts)
1. (1) newly, freshly, fresh, new -- (very recently; "they are newly married"; "newly raised
objections"; "a newly arranged hairdo"; "grass new washed by the rain"; "a freshly cleaned floor";
"we are fresh out of tomatoes")
--- WordNet end ---