Hsp40 Chaperones Promote Degradation of the hERG Potassium Channel

Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG.

The human ether-a-gogo-related gene (hERG) encodes the alpha subunit of the cardiac potassium current IKr. Several mutations in hERG produce trafficking-deficient channels that may cause hereditary long-QT syndrome and sudden cardiac death. Although hERG currents have been studied extensively, little is known about the proteins involved in maturation and trafficking of hERG. Using immunoprecipi...

Ion Conduction through the hERG Potassium Channel

The inward rectifier voltage-gated potassium channel hERG is of primary importance for the regulation of the membrane potential of cardiomyocytes. Unlike most voltage-gated K(+)-channels, hERG shows a low elementary conductance at physiological voltage and potassium concentration. To investigate the molecular features underlying this unusual behavior, we simulated the ion conduction through the...

Antidepressant-induced ubiquitination and degradation of the cardiac potassium channel hERG.

The most common cause for adverse cardiac events by antidepressants is acquired long QT syndrome (acLQTS), which produces electrocardiographic abnormalities that have been associated with syncope, torsade de pointes arrhythmias, and sudden cardiac death. acLQTS is often caused by direct block of the cardiac potassium current I(Kr)/hERG, which is crucial for terminal repolarization in human hear...

hERG potassium channel inhibition by ivabradine requires channel gating.

Toward a consensus model of the HERG potassium channel.

Malfunction of hERG potassium channels, due to inherited mutations or inhibition by drugs, can cause long QT syndrome, which can lead to life-threatening arrhythmias. A three-dimensional structure of hERG is a prerequisite to understand the molecular basis of hERG malfunction. To achieve a consensus model, we carried out an extensive analysis of hERG models based on various alignments of helix ...