Details

Autor(en) / Beteiligte

• Sahoo, Nirakar
• Goradia, Nishit
• Ohlenschläger, Oliver
• Schönherr, Roland
• Friedrich, Manfred
• Plass, Winfried
• Kappl, Reinhard
• Hoshi, Toshinori
• Heinemann, Stefan H

Titel

Heme impairs the ball-and-chain inactivation of potassium channels

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2013-10, Vol.110 (42), p.E4036-E4044

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• Fine-tuned regulation of K ⁺ channel inactivation enables excitable cells to adjust action potential firing. Fast inactivation present in some K ⁺ channels is mediated by the distal N-terminal structure (ball) occluding the ion permeation pathway. Here we show that Kv1.4 K ⁺ channels are potently regulated by intracellular free heme; heme binds to the N-terminal inactivation domain and thereby impairs the inactivation process, thus enhancing the K ⁺ current with an apparent EC ₅₀ value of ∼20 nM. Functional studies on channel mutants and structural investigations on recombinant inactivation ball domain peptides encompassing the first 61 residues of Kv1.4 revealed a heme-responsive binding motif involving Cys13:His16 and a secondary histidine at position 35. Heme binding to the N-terminal inactivation domain induces a conformational constraint that prevents it from reaching its receptor site at the vestibule of the channel pore.