IndraLab

Statements


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reach
"The mechanisms of BrS induced by amitriptyline were related to Nav1.5 trafficking and could be explained by the disrupted interaction of ankyrin-G, dystrophin and Nav1.5."

sparser
"Impaired Nav1.5 trafficking, regulated by Nav1.5-ankyrin-G and Nav1.5-dystrophin interaction, was suggested to be the mechanism related to such a long-term effect."

reach
"Although there is a long distance between these two binding sites on the primary sequence, the spatial proximity may exist to provide the necessary conditions for amitriptyline to impair the interaction between Nav1.5 and ankyrin-G."

sparser
"Thus, an additional role for Nav-beta subunits to regulate the AnkG/Nav1.5/K ATP complex is a real but unexplored possibility."

sparser
"A mutation in SCN5A (E1053K) discovered in a patient with BrS disrupts association of SCN5A with ankyrin-G, resulting in decreased I Na [ xref ]."

sparser
"Co-immunoprecipitation experiments were used to test the Nav1.5-ankyrin-G interaction and Nav1.5-dystrophin interaction."

sparser
"Such an in vivo model would also be able to address the question of whether disrupted AnkG/Nav1.5/K ATP interaction affects the ICD structure."

sparser
"The underlying mechanisms involved the impairment of Nav1.5 trafficking, which could be regulated by the Nav1.5-ankyrin-G interaction and Nav1.5-dystrophin interaction."

sparser
"Furthermore, we observed less co-localization and weaker binding between Nav1.5 and ankyrin-G or dystrophin after the long-term treatments with amitriptyline, indicating the disrupted Nav1.5-ankyrin-G interaction and Nav1.5-dystrophin interaction induced by amitriptyline."

reach
"These results suggested that the interaction between Nav1.5 and ankyrin-G or dystrophin could be weakened by the long-term effect of amitriptyline."

sparser
"An in vivo model with disrupted AnkG/Nav1.5/K ATP interaction would be ideal to address effects in cardiomyopathies or in clinically relevant arrhythmias."

sparser
"Although there is a long distance between these two binding sites on the primary sequence, the spatial proximity may exist to provide the necessary conditions for amitriptyline to impair the interaction between Nav1.5 and ankyrin-G. On the other hand, we discovered that the long-term effect of amitriptyline could destroy the Nav1.5-dystrophin interaction."

reach
"As deduced from these findings, the novel mechanism responsible for the long-term blockade effect of amitriptyline on Nav1.5 was the impairment of Nav1.5 trafficking.Furthermore, we observed less co-localization and weaker binding between Nav1.5 and ankyrin-G or dystrophin after the long-term treatments with amitriptyline, indicating the disrupted Nav1.5-ankyrin-G interaction and Nav1.5-dystrophin interaction induced by amitriptyline."

reach
"Co-immunoprecipitation experiments further testified that the combination of Nav1.5 and ankyrin-G or dystrophin was severely weakened after long-term treatments to amitriptyline, implying the failed interaction between Nav1.5 and ankyrin-G or dystrophin."