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VRAC - "The role of LRRC8 in the hypotonic stress response of human keratinocytes"

icon sp96   SyncroPatch 384  icon pl   Patchliner application note:   logo pdf   (1.7 MB)


The human skin is constantly exposed to various stress factors such as temperature changes, mechanical stress, different humidity levels, air pollution or radiation. These factors can have a tremendous impact on the skin and can contribute to barrier disruption and inflammation, dry and fragile skin as well as premature ageing. Recent advances in different research areas point to an important role of LRRC8 volume regulated anion channels (VRACs) in a plethora of different physiological processes. The function of LRRC8 has been characterized in human keratinocytes and in the native human epidermis and the LRRC8 ion channel has been proposed to be a novel molecular target to modulate keratinocyte differentiation in a recent patent.

LRRC8A (also named SWELL1) has been identified as the first essential component of VRACs in various cell types. LRRC8A is composed of four transmembrane domains and a C-terminal domain containing up to 17 leucine-rich repeats. Together with four additional LRRC8 family members (LRRC8B-E) it assembles into hetero-hexameric complexes. Interestingly, the LRRC8 subunit composition differs between cell types and influences VRAC properties such as inactivation kinetics, voltage-dependence and selectivity of the transported osmolyte. The generation of LRRC8A-/- knockout HaCaT keratinocytes have provided evidence for the essential function of LRRC8A in hypotonic stress response of human keratinocytes.

In this Application Note we show electrophysiological data from WT and LRRC8A-/- knockout HaCaT keratinocytes which corroborate the essential function of LRRC8A in keratinocytes.

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