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Cambridge, United Kingdom

Hill A.E.,Physiological Laboratory | Shachar-Hill Y.,Michigan State University
Journal of Membrane Biology | Year: 2015

Regulation of cell volume is central to homeostasis. It is assumed to begin with the detection of a change in water potential across the bounding membrane, but it is not clear how this is accomplished. While examples of general osmoreceptors (which sense osmotic pressure in one phase) and stretch-activated ion channels (which require swelling of a cell or organelle) are known, effective volume regulation requires true transmembrane osmosensors (TMOs) which directly detect a water potential difference spanning a membrane. At present, no TMO molecule has been unambiguously identified, and clear evidence for mammalian TMOs is notably lacking. In this paper, we set out a theory of TMOs which requires a water channel spanning the membrane that excludes the major osmotic solutes, responds directly without the need for any other process such as swelling, and signals to other molecules associated with the magnitude of changing osmotic differences. The most likely molecules that are fit for this purpose and which are also ubiquitous in eukaryotic cells are aquaporins (AQPs). We review experimental evidence from several systems which indicates that AQPs are essential elements in regulation and may be functioning as TMOs; i.e. the first step in an osmosensing sequence that signals osmotic imbalance in a cell or organelle. We extend this concept to several systems of current interest in which the cellular involvement of AQPs as simple water channels is puzzling or counter-intuitive. We suggest that, apart from regulatory volume changes in cells, AQPs may also be acting as TMOs in red cells, secretory granules and microorganisms. © 2015, Springer Science+Business Media New York.

Floyd R.V.,Physiological Laboratory | Wray S.,Physiological Laboratory | Martin-Vasallo P.,University of La Laguna | Mobasheri A.,Musculoskeletal Research Group
Annals of Anatomy | Year: 2010

FXYD proteins have been proposed to function as regulators of Na, K-ATPase function by lowering affinities of the system for potassium and sodium. However, their distribution in normal human tissues has not been studied. We have therefore used immunohistochemistry and semi-quantitative histomorphometric analysis to determine the relative expression at the protein level and distribution of FXYD1 (phospholemman) and FXYD2 (γ subunit of Na, K-ATPase) in human Tissue MicroArrays (TMAs). Expression of FXYD1 was abundant in heart, kidney, placenta, skeletal muscle, gastric and anal mucosa, small intestine and colon. Lower FXYD1 expression was detected in uterine, intestinal and bladder smooth muscle, choroid plexus, liver, gallbladder, spleen, breast, prostate and epididymis. The tissue distribution of FXYD2 was less extensive compared to that of FXYD1. There was an abundant expression in kidney and choroid plexus and moderate expression in placenta, amniotic membranes, breast epithelium, salivary glands, pancreas and uterine endometrium. Weaker FXYD2 expression was detected in the adrenal medulla, liver, gallbladder, bladder and pancreas. The common denominator in the distribution of FXYD1 and FXYD2 was expression in highly active transport epithelia of the kidney, choroid plexus, placenta and salivary glands. This study reveals, in human tissues, the specific expression of FXYD proteins, which may associate with Na, K-ATPase in selected cell types and modulate its catalytic properties. © 2009 Elsevier GmbH. All rights reserved.

Matthews G.D.K.,Physiological Laboratory | Huang C.L.-H.,Physiological Laboratory | Huang C.L.-H.,University of Cambridge | Sun L.,Mount Sinai School of Medicine | Zaidi M.,Mount Sinai School of Medicine
Annals of the New York Academy of Sciences | Year: 2011

Translational medicine must increasingly turn its attention to the aging population and the musculoskeletal deterioration that it entails. The latter involves the integrated function of both muscle and bone. Musculoskeletal science has an established interest in such problems in relationship to osteoporosis of bone. The introductory concepts in this paper consider the extent to which loss of muscle mass and function, or sarcopenia, will be the next major translational target. Its epidemiology shows parallels with that of osteoporosis, and the two tissues have a close functional relationship. Its etiology likely involves a loss of motor units combined with cellular signaling and endocrine changes. Finally, the possibility of modification of these physiological changes in the context of management of the sarcopenic condition is considered. © 2011 New York Academy of Sciences.

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