K⁺ pump: From caterpillar midgut to human cochlea

详细信息	查看全文 | 推荐本文 |

• 作者：William R. Harvey^a ; ^c ; ^d ; ^e ; Minghui A. Xiang^b ; ^c ; ^{Minghui.Xiang@jax.ufl.edu} ; ^{mh_xiang@yahoo.com}
• 关键词：Plasma membrane Ca2+ATPase 2 (PMCA2) ; H+ V-ATPase ; K+/H+ Antiporter 1 (KHA1) ; K+/H+ Antiporter 2 (KHA2) ; NHA2 ; Hair cells ; Hair bundles ; Stereocilia ; Supporting cells ; Stria vascularis
• 刊名：Journal of Insect Physiology
• 出版年：2012
• 期刊代码：92_00221910
• 类别：bio
• 出版时间：April, 2012
• 卷：58
• 期：4
• 页码：590-598
• 文件大小：1308 K

摘要

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 20,000 cycles/sec (20 kHz) are not well understood. Sound is transduced to electrical signals by stereocilia of hair cells by influx of Ca²⁺ and K⁺ as the 鈥渢ransducer channel鈥?opens transiently and reduces the 鈭?0 mV (endolymph positive) endocochlear potential (EP) by 鈭?0 mV 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 20 kHz 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 鈭?0 nanometers with travel time of 鈭?0 渭s, which is fast enough to account for the 50 渭s open/close time for 20 kHz 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 鈭?00 mV, K⁺ secretion into a K⁺ rich compartment and reversible inhibition by anoxia. The key role of the Type V K⁺ pump in generating the EP was recognized by Sellick and Bock in 1974 and others but has disappeared from the hearing literature during the past decades. Its revival here is based on immunolocalization of KHA2 in the stereocilial membrane and Gillespie鈥檚 generously shared mass spectroscopy evidence that all but one of the V₁ ATPase subunits are detected in isolated chicken stereocilia but V_o and KHAs are not detected (implying that KHAs must be in the membrane). The new model proposed in the present paper could lead to important changes in our understanding of sensory physiology.