Cortisone, a steroid hormone produced by the adrenal gland, can unexpectedly separate potassium channel subunits that aid membrane depolarization and coordinated muscle contraction. A study online this week in Nature Chemical Biology raises questions as to whether this type of control might have implications for human disease including ataxia and cardiac arrhythmia and simultaneously provides a chemical scaffold for future drug development.
The cell membrane separates intra and extracellular environments. After a change in the charge distribution across the membrane required for muscle contraction, potassium channels of the Shaker family open temporarily and relieve the charge imbalance by creating a pore that releases potassium ions.
Ming Zhou and colleagues performed both structural analyses and functional studies to demonstrate that the hormone binds between channel subunits, separating them, allowing the channel to remain open. Discovery of a hormone that dissociates channel subunits was surprising since few small molecules have been identified that disrupt other protein-protein interactions.