ABSTRACT
Only a handful of ion channel proteins are selective for nature’s smallest ion, H+ (hydrogen ion or proton). One of these, Hv1, is voltage-gated and mediates H+ efflux from cells. Hv1 is crucial for normalizing intracellular pH during the respiratory burst in phagocytic leukocytes. Otopetrins (OTOPs) constitute an unrelated family of voltage-independent proton channels. OTOP1 is required for sour taste transduction and mineralization of vestibular otoconia, but the functions of OTOP2 and OTOP3, which are expressed in the digestive system, are not well understood. Essential features of Hv1 and OTOP channel function, structure and cellular physiology are described in this chapter. Understanding the structural bases of proton-selective permeation in OTOP and Hv1 channels presents unique challenges, and here we highlight fundamental mechanistic questions that remain unanswered.
