Tags

Type your tag names separated by a space and hit enter

K+ pump: from caterpillar midgut to human cochlea.
J Insect Physiol. 2012 Apr; 58(4):590-8.JI

Abstract

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 B(1) 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 Ca(2+) and K(+) as the "transducer channel" opens transiently and reduces the ∼90 mV (endolymph positive) endocochlear potential (EP) by ∼20 mV as the receptor potential. The EP as well as concentrations of Ca(2+), H(+) and K(+) must remain constant to produce reliable signals. Ca(2+) entry is balanced by Ca(2+) exit via a plasma membrane Ca(2+) ATPase (PMCA2a) but the Ca(2+) 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, Ca(2+), 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 ∼10 μs, which is fast enough to account for the 50 μs 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 ∼100 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's generously shared mass spectroscopy evidence that all but one of the V(1) 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.

Authors+Show Affiliations

Whitney Mosquito Biology Group, University of Florida, St. Augustine, FL 32080, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22410306

Citation

Harvey, William R., and Minghui A. Xiang. "K+ Pump: From Caterpillar Midgut to Human Cochlea." Journal of Insect Physiology, vol. 58, no. 4, 2012, pp. 590-8.
Harvey WR, Xiang MA. K+ pump: from caterpillar midgut to human cochlea. J Insect Physiol. 2012;58(4):590-8.
Harvey, W. R., & Xiang, M. A. (2012). K+ pump: from caterpillar midgut to human cochlea. Journal of Insect Physiology, 58(4), 590-8. https://doi.org/10.1016/j.jinsphys.2012.03.001
Harvey WR, Xiang MA. K+ Pump: From Caterpillar Midgut to Human Cochlea. J Insect Physiol. 2012;58(4):590-8. PubMed PMID: 22410306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - K+ pump: from caterpillar midgut to human cochlea. AU - Harvey,William R, AU - Xiang,Minghui A, Y1 - 2012/03/09/ PY - 2012/01/29/received PY - 2012/02/29/revised PY - 2012/03/02/accepted PY - 2012/3/14/entrez PY - 2012/3/14/pubmed PY - 2012/7/11/medline SP - 590 EP - 8 JF - Journal of insect physiology JO - J Insect Physiol VL - 58 IS - 4 N2 - 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 B(1) 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 Ca(2+) and K(+) as the "transducer channel" opens transiently and reduces the ∼90 mV (endolymph positive) endocochlear potential (EP) by ∼20 mV as the receptor potential. The EP as well as concentrations of Ca(2+), H(+) and K(+) must remain constant to produce reliable signals. Ca(2+) entry is balanced by Ca(2+) exit via a plasma membrane Ca(2+) ATPase (PMCA2a) but the Ca(2+) 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, Ca(2+), 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 ∼10 μs, which is fast enough to account for the 50 μs 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 ∼100 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's generously shared mass spectroscopy evidence that all but one of the V(1) 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. SN - 1879-1611 UR - https://www.unboundmedicine.com/medline/citation/22410306/K+_pump:_from_caterpillar_midgut_to_human_cochlea_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-1910(12)00048-0 DB - PRIME DP - Unbound Medicine ER -