ENDOTHELIN-MEDIATED CALCIUM RESP´NSES IN SUPRAOPTIC NUCLEUS ASTROCYTES INFLUENCE MAGNOCELLULAR NEUROSECRETORY FIRING ACTIVITY

FILOSA, JESSICA; NASKAR, KRISHNA; PERFUME GUADALUPE; IDDINGS, JENNIFER; BIANCARDI, VINICIA; VATTA, MARCELO; STERN, JAVIER

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Año: 2011

0953-8194

Abstract In addition to their peripheral vasoactive effects, accumulating evidence supports an important role for endothelins (ETs) in the regulation of the hypothalamic magnocellular neurosecretory system, which produces and releases the neurohormones vasopressin (VP) and oxytocin (OT). Still, the precise cellular substrates, loci and mechanisms underlying ETs actions on the magnocellular system are poorly understood. In the present study, we combined patch-clamp electrophysiology, confocal Ca2+ 8 imaging and immunohistochemistry to study ETs actions on supraoptic nucleus (SON) magnocellular neurosecretory neurons and astrocytes. Our studies show that ET-1 evoked rises in [Ca2+10 ]i levels in SON astrocytes (but not neurons), an effect largely mediated by activation of ETB receptors and mobilization of thapsigargin-sensitive Ca2+ 2+ 8 imaging and immunohistochemistry to study ETs actions on supraoptic nucleus (SON) magnocellular neurosecretory neurons and astrocytes. Our studies show that ET-1 evoked rises in [Ca2+10 ]i levels in SON astrocytes (but not neurons), an effect largely mediated by activation of ETB receptors and mobilization of thapsigargin-sensitive Ca2+ 2+10 ]i levels in SON astrocytes (but not neurons), an effect largely mediated by activation of ETB receptors and mobilization of thapsigargin-sensitive Ca2+ B receptors and mobilization of thapsigargin-sensitive Ca2+  stores. The presence of ETB receptors in SON astrocytes was also verified immunohistochemically. ETB receptor activation either increased (75%) or decreased (25%) SON firing activity, both in VP and putative OT neurons, effects that were prevented when slices were preincubated in glutamate receptor blockers or NOS blockers, respectively. Moreover, ETB mediated effects in SON neurons were also prevented by a gliotoxin compound, and when changes in [Ca2+17 ]i were prevented with bath applied BAPTA-AM or thapsigargin. immunohistochemically. ETB receptor activation either increased (75%) or decreased (25%) SON firing activity, both in VP and putative OT neurons, effects that were prevented when slices were preincubated in glutamate receptor blockers or NOS blockers, respectively. Moreover, ETB mediated effects in SON neurons were also prevented by a gliotoxin compound, and when changes in [Ca2+17 ]i were prevented with bath applied BAPTA-AM or thapsigargin. SON firing activity, both in VP and putative OT neurons, effects that were prevented when slices were preincubated in glutamate receptor blockers or NOS blockers, respectively. Moreover, ETB mediated effects in SON neurons were also prevented by a gliotoxin compound, and when changes in [Ca2+17 ]i were prevented with bath applied BAPTA-AM or thapsigargin. changes in [Ca2+17 ]i were prevented with bath applied BAPTA-AM or thapsigargin. Conversely, intracellular Ca2+ 18 chelation in the recorded SON neurons failed to block ETB- mediated effects. In summary, our results indicate that ETB receptor activation in SON astrocytes induces mobilization of [Ca2+]i, likely resulting in the activation of glutamate and nitric oxide signaling pathways, evoking in turn excitatory and inhibitory SON neuronal responses, respectively. Taken together, our study supports an important role for astrocytes in mediating ETs actions on the magnocellular neurosecretory system.