In addition to the suspected GPCR, there are several additional proposed mechanisms for the bioactivity of EETs in the nervous system [40]. EETs activate TRPV4 channels [47] stimulating rapid calcium release events (calcium sparks) that activate potassium channels and the hyperpolarization of cells [47–49]. In smooth muscle cells, specific regioisomers of EETs also activate ATP-sensitive potassium channels in both a protein kinase A (PKA) and G protein related manner [50, 51]. It should be noted that the many studies providing this mechanistic evidence have been conducted in endothelial and smooth muscle cells of vascular tissues. Spector has made a strong argument that there likely are multiple GPCRs modulated by EFAs but also other regulatory systems including ion channels are regulated by these molecules (Personal communication). The effect of EETs in neural tissues is comparatively unexplored but is expected to share these mechanisms.
