TRPC1-mediated Ca2+ and Na+ signalling in astroglia: Differential filtering of extracellular cations

Abstract

Canonical transient receptor potential 1 (TRPC1) plasmalemmal cation channels mediate Ca2+ and Na+ fluxes and control respective cytoplasmic ion signals in rat cortical astrocytes. Mechanical stimulation of astrocytes results in an increase in the levels of cytosolic Ca2+ and Na+ that are in part due to entry of extracellular cations through TRPC1 containing channels. Inhibition of the TRPC1 pore with an antibody against its selective filter reduced cytosolic Ca2+ accumulation caused by mechanical stimulation. In contrast, this immunological treatment increased the cytosolic Na+ peak accumulation induced by mechanical stimulation. We propose that TRPC channels are amenable to changes in selective filtering, as mutations in previous studies and antibody binding in our present study differentially affect the flux of Ca2+ and Na+. TRPC1 containing channels might represent focal points for co-ordination of Ca2+ and Na+ signalling in astroglia and this can have consequences on Ca2+- and Na+-dependent processes such as regulated exocytosis and lactate production, respectively, which in turn can modulate neuronal synaptic transmission.