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Induction of autoimmune response to the extracellular loop of the HERG channel pore induces QTc prolongation in guinea-pigs
Induction of autoimmune response to the extracellular loop of the HERG channel pore induces QTc prolongation in guinea-pigs
- Source :
- The Journal of physiology. 594(21)
- Publication Year :
- 2016
-
Abstract
- Channelopathies of autoimmune origin are novel and are associated with corrected QT (QTc) prolongation and complex ventricular arrhythmias.We have recently demonstrated that anti‐SSA/Ro antibodies from patients with autoimmune diseases and with QTc prolongation on the ECG target the human ether‐à‐go‐go‐related gene (HERG) K+ channel by inhibiting the corresponding current, I Kr, at the pore region.Immunization of guinea‐pigs with a peptide (E‐pore peptide) corresponding to the extracellular loop region connecting the S5 and S6 segments of the HERG channel induces high titres of antibodies that inhibit I Kr, lengthen the action potential and cause QTc prolongation on the surface ECG. In addition, anti‐SSA/Ro‐positive sera from patients with connective tissue diseases showed high reactivity to the E‐pore peptide.The translational impact is the development of a peptide‐based approach for the diagnosis and treatment of autoimmune‐associated long QT syndrome.
Details
- ISSN :
- 14697793
- Volume :
- 594
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- The Journal of physiology
- Accession number :
- edsair.pmid.dedup....ba1e3b86750b21bbf5f087e8b6903cda