Histamine-induced Ca2+ signalling is mediated by TRPM4 channels in human adipose-derived stem cells

Abstract

Intracellular Ca2+ oscillations are frequently observed during stem cell differentiation, and there is evidence that it may control adipogenesis. The transient receptor potential melastatin 4 channel (TRPM4) is a key regulator of Ca2+ signals in excitable and non-excitable cells. However, its role in human adipose-derived stem cells (hASCs), in particular during adipogenesis, is unknown. We have investigated TRPM4 in hASCs and examined its impact on histamine-induced Ca2+ signalling and adipogenesis. Using reverse transcription (RT)–PCR, we have identified TRPM4 gene expression in hASCs and human adipose tissue. Electrophysiological recordings revealed currents with the characteristics of those reported for the channel. Furthermore, molecular suppression of TRPM4 with shRNA diminished the Ca2+ signals generated by histamine stimulation, mainly via histamine receptor 1 (H1) receptors. The increases in intracellular Ca2+ were due to influx via voltage-dependent Ca2+ channels (VDCCs) of the L-type (Cav1.2) and release from the endoplasmic reticulum. Inhibition of TRPM4 by shRNA inhibited adipogenesis as indicated by the reduction in lipid droplet accumulation and adipocyte gene expression. These results suggest that TRPM4 is an important regulator of Ca2+ signals generated by histamine in hASCs and is required for adipogenesis.