K+ pump: From caterpillar midgut to human cochlea

[Display omitted] ► The endocochlear potential in stereocilia is deduced to be a K+ pump potential. ► The K+ pump is known to be an H+ V-ATPase: K+/H+ antiporter (KHA) pair. ► H+ V-ATPase and KHA are postulated to be in the plasma membrane of cochlear stereocilia. ► The K+ pump in hair-, supporting- and stria-cells is postulated to be an H+ V-ATPase: KHA pair. ► Ca2+, H+ and K+ are postulated to cycle rapidly in unstirred layers of cochlear stereocilia. Deafness is a serious condition that affects millions of people and can also lead to dementia. Moreover, Karet and associates reported in 1999 that mutations in the gene encoding H+ V-ATPase subunit B1 lead to deafness. Yet ionic flows that enable humans to hear high-pitched sounds at 20,000cycles/sec (20kHz) are not well understood. Sound is transduced to electrical signals by stereocilia of hair cells by influx of Ca2+ and K+ as the “transducer channel” opens transiently and reduces the ∼90mV (endolymph positive) endocochlear potential (EP) by ∼20mV as the receptor potential. The EP as well as concentrations of Ca2+, H+ and K+ must remain constant to produce reliable signals. Ca2+ entry is balanced by Ca2+ exit via a plasma membrane Ca2+ ATPase (PMCA2a) but the Ca2+ exit is coupled to H+ entry. Moreover, K+ entry is balanced by K+ exit via a long diffusion route through several channels which is too slow to account for 20kHz signaling. The problem is solved by a new hypothesis in which an H+ V-ATPase generates the EP and removes the H+ while a new K+/H+ antiporter uses the voltage to drive H+ back in and the K+ back out. In the new model, Ca2+, H+ and K+ cycle between unstirred layers on the endolymph- and cytoplasmic- borders of the stereocilial membrane through distances of ∼20 nanometers with travel time of ∼10μs, which is fast enough to account for the 50μs open/close time for 20kHz signaling. Central to this model is the hypothesis that a K+ pump which secretes K+ into a K+-rich compartment is composed of a voltage producing (electrogenic) H+ V-ATPase that is electrically coupled to a voltage-driven (electrophoretic) K+/nH+ antiporter (KHA). Conversely, for an H+ V-ATPase to secrete K+ into a K+ rich compartment, it must be coupled to a KHA. Richard Keynes reviewed evidence in 1969 that such a K+ pump, which he called a Type V pump, is present in the stria vascularis of cochlea and the goblet cell apical membrane of caterpillars. Its signature is a large outside positive potential of ∼100mV, K+ secre