Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA104

Poster Communications

Enhanced Ca2+ signalling and over-expression of STIM1 are characteristic of human eccrine sweat gland secretory coil cells isolated from hyperhidrotic individuals

R. L. Evans1, S. R. Johnstone2, M. Elias2, J. Roberston2, D. L. Bovell3, P. E. Martin2

1. Unilever Research & Development, Bebington, Wirral, United Kingdom. 2. Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom. 3. Weill-Cornell Medicine-Qatar, Doha, Qatar.


The condition of hyperhidrosis occurs when eccrine gland sweating exceeds that required for normal body temperature regulation. It can be primary (focal), where no underlying cause has been identified, or secondary (generalized), where an underlying cause is known. Primary hyperhidrosis typically occurs in the axillae, or on the forehead, palms and feet, and can be anxiety-inducing and disabling. The underlying cause of hyperhidrosis is largely unknown. Eccrine gland sweat production is initiated by a biphasic increase in the level of intracellular Ca2+ ([Ca2+]i) consisting of an initial agonist-induced release of Ca2+ from internal stores, followed by an influx of extracellular Ca2+, a process known as store-operated Ca2+ entry (SOCE)1. Recent studies of isolated human eccrine gland secretory coil cells have demonstrated that SOCE is regulated by the interaction of STIM and Orai proteins2. The aim of this study was to investigate the role of SOCE during hyperhidrosis, using eccrine sweat gland secretory coil cells from individuals with and without hyperhidrosis. Sweat glands were isolated from skin samples donated with consent3. Intracellular Ca2+ responses were studied using Ca2+ imaging techniques, and the relative expression of various proteins associated with SOCE determined by mRNA expression, Western blot analysis and immunofluorescence. SiRNA knockdown of STIM and Orai proteins, in conjunction with Ca2+ imaging of cells stimulated with the ER Ca2+-ATPase inhibitor thapsigargin (Tg), was used to determine the relative contributions of various SOCE proteins to fluid secretion by hyperhidrotic cells. Fluorescence imaging showed that the dose-response to stimulation with the muscarinic agonist carbachol was elevated at least 2-fold in hyperhidrotic eccrine gland secretory cells compared to those from non-hyperhidrotic cells. Expression of STIM1 mRNA was also significantly higher (~2-fold) in hyperhidrotic cells, whilst mRNA expression of the SOCE proteins Orai1, TRPC1, the muscarinic receptor m3, IP3 receptor isoforms 1,2 and 3, and the water channel AQP5, were not significantly elevated. Over-expression of STIM1 was also confirmed at protein level by Western blotting and immunohistochemistry. STIM2 was not over-expressed. Ca2+ imaging of hyperhidrotic eccrine glands showed that Tg-induced SOCE was reduced ~90% in a STIM1 knockdown, and by ~79% in an Orai1 knockdown. This study suggests that the over-expression of STIM1 results in enhanced SOCE (and probably sweat secretion) in human hyperhidrotic eccrine gland secretory coil cells. Further mechanistic investigations will be required to fully determine the molecular physiology underlying this distressing human condition.

Where applicable, experiments conform with Society ethical requirements