Human sensory neurons may not only bridge a critical gap between drug discovery and clinical trials, but force a re-evaluation of basic assumptions about the mechanisms controlling primary afferent excitability.
Fatty acid analogues are interesting prototype compounds that may inspire the development of future IKs channel activators to treat patients with long QT syndrome caused by diverse arrhythmia-causing mutations in the IKs channel.
Independently gating ion channels typically act fast within milliseconds, but cooperative interactions within a cluster of channels allow for a memory of previous electrical activity for several seconds.
The biophysical diversity that is intrinsic to spiral ganglion neurons emerges as spatial gradients during early post-natal development and endures through subsequent maturation to likely contribute to sound intensity coding.
Analysis of conformational changes indicates that activation of acid-sensing ion channels involves protonation of diverse extracellular sites and interaction of interdomain loops with the upper ends of transmembrane helices.