Extracellular Kir2.1 < sup > C122Y < /sup > Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome

CONCLUSIONS: The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.PMID:38497220 | DOI:10.1161/CIRCRESAHA.123.323895

Source: Circulation Research - March 18, 2024 Category: Cardiology Authors: Francisco M Cruz Álvaro Macías Ana I Moreno-Manuel Lilian K Guti érrez Mar ía Linarejos Vera-Pedrosa Isabel Mart ínez-Carrascoso Patricia S ánchez Pérez Juan Manuel Ruiz Robles Francisco J Berm údez-Jiménez Aitor D íaz-Agustín Fernando Mart ín Source Type: research