Genetic deletion of Kir6.2 caused arrhythmia and sudden death during vigorous sympathetic challenge, which was preventable by calcium-channel blockade.
Does genetic deletion of Kir6.2 cause arrhythmia and sudden death during sympathetic challenge in a preclinical model?
Kir6.2 is essential for cardiac adaptation to sympathetic stress, and its absence leads to fatal arrhythmias that can be prevented by calcium-channel blockade.
Reaction to stress requires feedback adaptation of cellular functions to secure a response without distress, but the molecular order of this process is only partially understood. Here, we report a previously unrecognized regulatory element in the general adaptation syndrome. Kir6.2, the ion-conducting subunit of the metabolically responsive ATP-sensitive potassium (K(ATP)) channel, was mandatory for optimal adaptation capacity under stress. Genetic deletion of Kir6.2 disrupted K(ATP) channel-dependent adjustment of membrane excitability and calcium handling, compromising the enhancement of cardiac performance driven by sympathetic stimulation, a key mediator of the adaptation response. In the absence of Kir6.2, vigorous sympathetic challenge caused arrhythmia and sudden death, preventable by calcium-channel blockade. Thus, this vital function identifies a physiological role for K(ATP) channels in the heart.
Zingman et al. (Mon,) conducted a other in Sympathetic stress. Genetic deletion of Kir6.2 vs. Presence of Kir6.2 was evaluated on Arrhythmia and sudden death. Genetic deletion of Kir6.2 caused arrhythmia and sudden death during vigorous sympathetic challenge, which was preventable by calcium-channel blockade.