A mechanically activated TRPC1-like current in white adipocytes

Abstract

Ca²⁺ impacts a large array of cellular processes in every known cell type. In the white adipocyte, Ca²⁺ is involved in regulation of metabolic processes such as lipolysis, glucose uptake and hormone secretion. Although the importance of Ca²⁺ in control of white adipocyte function is clear, knowledge is still lacking regarding the control of dynamic Ca²⁺ alterations within adipocytes and mechanisms inducing intracellular Ca²⁺ changes remain elusive. Own work has recently demonstrated the existence of store-operated Ca²⁺ entry (SOCE) in lipid filled adipocytes. We defined stromal interaction molecule 1 (STIM1) and the calcium release-activated calcium channel protein 1 (ORAI1) as the key players involved in this process and we showed that the transient receptor potential (TRP) channel TRPC1 contributed to SOCE. Here we have aimed to further characterised SOCE in the white adipocyte by use of single cell whole-cell patch clamp recordings. The electrophysiological measurements show the existence of a seemingly constitutively active current that is inhibited by known store-operated Ca²⁺ channel (SOCC) blockers. We demonstrate that the mechanical force applied to the plasma membrane upon patching leads to an elevation of the cytoplasmic Ca²⁺ concentration and that this elevation can be reversed by SOCC antagonists. We conclude that a mechanically activated current with properties similar to TRPC1 is present in white adipocytes. Activation of TRPC1 by membrane tension/stretch may be specifically important for the function of this cell type, since adipocytes can rapidly increase or decrease in size.

Keywords: Intracellular Ca(2+); Ion channels; Mechanical activation; Store-operated Ca(2+) entry; TRPC1; White adipocytes.