Extracellular hemin is a reverse use-dependent gating modifier of cardiac voltage-gated Na⁺ channels.

ABSTRACT: Heme (Fe²⁺-protoporphyrin IX) is a well-known protein prosthetic group; however, heme and hemin (Fe³⁺-protoporphyrin IX) are also increasingly viewed as signaling molecules. Among the signaling targets are numerous ion channels, with intracellular-facing heme-binding sites modulated by heme and hemin in the sub-µM range. Much less is known about extracellular hemin, which is expected to be more abundant, in particular after hemolytic insults. Here we show that the human cardiac voltage-gated sodium channel hNa_V1.5 is potently inhibited by extracellular hemin (IC ₅₀ ≈ 80 nM), while heme, dimethylhemin, and protoporphyrin IX are ineffective. Hemin is selective for hNa_V1.5 channels: hNa_V1.2, hNa_V1.4, hNa_V

SUBMITTER: Gessner G 

PROVIDER: S-EPMC9661527 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature