Sequential and opposite regulation of two outward K+ currents by ET-1 in cultured striatal astrocytes

In the brain, astrocytes represent a major target for endothelins (ETs), a family of peptides that can be released by several cell types and that have potent and multiple effects on astrocytic functions. Four types of K+ currents (I-K) were detected in various proportions by patch-clamp recordings of cultured striatal astrocytes, including the A-type I-K, the inwardly rectifying I-K IR, the Ca2+-dependent I-K (I-K Ca), and the delayed-rectified I-K (I-K DR). Variations in the shape of current-voltage relationships were related mainly to differences in the proportion of these currents. ET-1 was found to regulate with opposite effects the two more frequently recorded outward K+ currents in striatal astrocytes. Indeed, this peptide induced an initial activation of I-K Ca (composed of SK and BK channels) and a delayed long-lasting inhibition of I-K DR. In current-clamp recordings, the activation of I-K Ca correlated with a transient hyperpolarization, whereas the inhibition of I-K DR correlated with a sustained depolarization. These ET-1-induced sequential changes in membrane potential in astrocytes may be important for the regulation of voltage gradients in astrocytic networks and the maintenance of K+ homeostasis in the brain microenvironment.