V-ATPASE LOCATION IN HUMAN ECCRINE SWEAT GLANDS Bovell, DL, Clunes, MT, Elder, HY*, Lindsay, S and Roussa E#.

School of Biological and Biomedical Sciences, Glasgow Caledonian University, UK, *Institute of Biomedical and Life Sciences, University of Glasgow, UK and #School of Biological Sciences, University of Manchester, UK Sweat formation involves secretion of an initial, isotonic, plasma-like fluid, followed by salt reabsorption. Reddy & Quinton (3) recognised that a second reabsorptive mechanism, in addition to the basolaterally located, sodium pump-driven mechanism, was necessary to explain the acidity (down to pH 4) and very low salt concentration (as low as 5 mM NaCl) found in normal sweat at low secretory rates. They proposed that HCO3–/Cl– exchange, brings Cl– into the reabsorptive cells against the electrochemical driving force, and predicted the presence of luminal proton pumps as the driving mechanism; carbonic anhydrase (CA) is known to be present, particularly in the luminal duct cells (2). The presence of V-ATPase proton pumps has been confirmed by immuno-cytochemistry (1), particularly strongly located to luminal duct cells. In that study, the finding also of strong expression of V-ATPase in the cytoplasm and luminal membrane of secretory epithelium was interesting as Na+/K+/2Cl– co-transport and the basolateral Na+/K+-ATPase hitherto seemed adequate to explain primary secretion. In the secretory coil, further V-ATPase Immuno-cytochemistry, with sensitivity increased by antigen retrieval, has shown that the proton pumps are predominantly located in the clear (nongranular) cells (Fig. 1). These mitochondria-rich cells are known to stain strongly for the active CAII (2) and are the cells primarily involved in fluid and electolyte secretion. It seems likely that there may be a second component to the secretory process involving the proton pump. Secretion could operate as a “push-pull” mechanism, the “push” provided by the sodium pump with the Na+/K+/2Cl- co-transporter raising [Cl-] and [K+] above their equilibrium potentials, and the “pull” provided by the proton pump, known to energise luminal membranes (4). Bicarbonate is known to be necessary for human sweat gland function (5) and other transport mechanisms are likely to be present in the luminal membranes to effect production of the normal primary secretion at >pH 7. Further work will test these speculations.
Fig.1.Immuno-cytochemical staining of secretory portions of normal glands for V-ATPase, as in Bovell et al. (1), but with sensitivity enhanced by antigen retrieval. The mosaic distribution of staining, mainly in the non-granular (clear) cells, recognisable by their characteristic appearance of broad base out and apex to the lumen, is apparent.

1. Bovell DL, Clunes MT, Roussa E, Burry J and Elder HY. Vacuolar-type H+-ATPase distribution in unstimulated and acetylcholine-activated isolated human eccrine sweat glands. Histochem J 32: 409-413, 2000. 2. Briggman JV, Tashian RE and Spicer SS. Immuno-cytochemical localization of carbonic anhydrase I and II in eccrine sweat glands from control subjects and patients with cystic fibrosis. Am J Path 112: 250-257, 1983. 3. Reddy MM & Quinton PM. Intracellular chloride activity: evidence of dual mechanisms of chloride absorption in sweat duct. Am J Physiol 267: C1136-C1144, 1994. 4. Wieczorek H, Brown D, Grinstein S, Ehrenfeld J and Harvey WR. Animal plasma membrane energization by protonmotive V-ATPases. BioEssays 21: 637-648, 1999 5. Wilson SM, Bovell DL, Elder HY, Jenkinson, DM and Pediani JD. The effect of removing external sodium upon the control of potassium (86Rb+) permeability in the isolated human sweat gland. Exp Physiol 75: 649-656, 1990. ______________________________________________________________________________________________ This work was funded by Unilever Research, approved by the ethics committee of North Glasgow University Health Trust and performed with the informed consent of patients.

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