Hsp40 chaperones promote degradation of the HERG potassium channel.

Loss of function mutations in the hERG (human ether-a-go-go related gene or KCNH2) potassium channel underlie the proarrhythmic cardiac long QT syndrome type 2. Most often this is a consequence of defective trafficking of hERG mutants to the cell surface, with channel retention and degradation at the endoplasmic reticulum. Here, we identify the Hsp40 type 1 chaperones DJA1 (DNAJA1/Hdj2) and DJA2 (DNAJA2) as key modulators of hERG degradation.

Co-chaperone FKBP38 promotes HERG trafficking.

The Long QT Syndrome is a cardiac disorder associated with ventricular arrhythmias that can lead to syncope and sudden death. One prominent form of the Long QT syndrome has been linked to mutations in the HERG gene (KCNH2) that encodes the voltage-dependent delayed rectifier potassium channel (I(Kr)). In order to search for HERG-interacting proteins important for HERG maturation and trafficking, we conducted a proteomics screen using myc-tagged HERG transfected into cardiac (HL-1) and non-cardiac (human embryonic kidney 293) cell lines.

Cardiopulmonary physiology and responses of ultramarathon athletes to prolonged exercise.

The purpose of this study was to determine the changes of pulmonary function and autonomic cardiovascular control after an ultramarathon and their relation to performance. Eight entrants to the Canadian National Championship 100-km running race participated in the study. Pulmonary function and 30-s maximum voluntary ventilation (MVV30s) tests were conducted one day before the race and within 5 minutes of race completion.