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Publication Abstract from PubMed

Voltage-gated K(+) (Kv) channels mediate the flow of K(+) across the cell membrane by regulating the conductive state of their activation gate (AG). Several Kv channels display slow C-type inactivation, a process whereby their selectivity filter (SF) becomes less or nonconductive. It has been proposed that, in the fast inactivation-removed Shaker-IR channel, the W434F mutation epitomizes the C-type inactivated state because it functionally accelerates this process. By introducing another pore mutation that prevents AG closure, P475D, we found a way to record ionic currents of the Shaker-IR-W434F-P475D mutant at hyperpolarized membrane potentials as the W434F-mutant SF recovers from its inactivated state. This W434F conductive state lost its high K(+) over Na(+) selectivity, and even NMDG(+) can permeate, features not observed in a wild-type SF. This indicates that, at least during recovery from inactivation, the W434F-mutant SF transitions to a widened and noncationic specific conformation.

The nonconducting W434F mutant adopts upon membrane depolarization an inactivated-like state that differs from wild-type Shaker-IR potassium channels.,Coonen L, Martinez-Morales E, Van De Sande DV, Snyders DJ, Cortes DM, Cuello LG, Labro AJ Sci Adv. 2022 Sep 16;8(37):eabn1731. doi: 10.1126/sciadv.abn1731. Epub 2022 Sep , 16. PMID:36112676^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.