Modulatory actions of endothelins on neural-glial communication in the

KRISHNA N; PERFUME G; VATTA MS; FILOSA J; STERN J

MONTREAL, CANADA

Congreso; 11th International Conference on Endothelin; 2009

AMERICAN PHYSIOLOGICAL SOCIETY

In addition to being potent vasoactive peptides, endothelins (ETs) act as neuromodulators within the CNS, influencing among others, vasopressin (VP) secretion. Still, the precise underlying mechanism for this effect is largely unknown. Given that ET receptors are present both in neurons and astrocytes; in this study we evaluated the effects of ET receptor activation on both supraoptic nucleus (SON) neurosecretory neurons and astrocytes. Patch-clamp recordings from SON neurons in a slice preparation showed that bath application of the ETB receptor agonist sarafatoxin 6c (100 nM) diminished ongoing firing frequency (~70%) of SON neurons with a latency of ~ 9 minutes. In addition, ET-1 (100 nM) and sarafotoxin 6c increased intracellular calcium [Ca2+]i in SON astrocytes (~80% change in F/F0), an effect blocked in the presence of thapsigargin but not Ca2+-free media. On the other hand, ET receptor activation failed to induce [Ca2+]I neuronal changes. Finally,  preincubation of SON slices with the selective gliotoxin Laminoadiptic acid (0.25 mM) prevented ET-induced effects on SON neuronal firing activity. Altogether, these results show that ET receptor activation increased [Ca2+]i in SON astrocytes, and likely active a mechanism that lead to inhibition of SON  neuronal activity. Our study supports an important role for ET in the neuronal-glial communication in the magnocellular neurosecretory sytem. (Supported by AHA 0640092N to JES).