Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity

Jessica Andrea Filosa, K. Naskar, G. Perfume, J. A. Iddings, V. C. Biancardi, M. S. Vatta, J. E. Stern

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 the actions of ETs on the magnocellular system are poorly understood. In the present study, we combined patch-clamp electrophysiology, confocal Ca 2+ imaging and immunohistochemistry to study the actions of ETs on supraoptic nucleus (SON) magnocellular neurosecretory neurones and astrocytes. Our studies show that ET-1 evoked rises in [Ca 2+] i levels in SON astrocytes (but not neurones), an effect largely mediated by the activation of ET B receptors and mobilisation of thapsigargin-sensitive Ca 2+ stores. The presence of ET B receptors in SON astrocytes was also verified immunohistochemically. ET B receptor activation either increased (75%) or decreased (25%) SON firing activity, both in VP and putative OT neurones, and these effects were prevented when slices were preincubated in glutamate receptor blockers or nitric oxide synthase blockers, respectively. Moreover, ET B-mediated effects in SON neurones were also prevented by a gliotoxin compound, and when changes in [Ca 2+] i were prevented with bath-applied BAPTA-AM or thapsigargin. Conversely, intracellular Ca 2+ chelation in the recorded SON neurones failed to block ET B-mediated effects. In summary, our results indicate that ET B receptor activation in SON astrocytes induces the mobilisation of [Ca 2+] i, likely resulting in the activation of glutamate and nitric oxide signalling pathways, evoking in turn excitatory and inhibitory SON neuronal responses, respectively. Taken together, our study supports an important role for astrocytes in mediating the actions of ETs on the magnocellular neurosecretory system.

Original languageEnglish (US)
Pages (from-to)378-392
Number of pages15
JournalJournal of Neuroendocrinology
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2012

Fingerprint

Supraoptic Nucleus
Endothelins
Astrocytes
Endothelin B Receptors
Calcium
Neurons
Neurosecretory Systems
Thapsigargin
Oxytocin
Vasopressins
Gliotoxin
Electrophysiology
Glutamate Receptors
Endothelin-1
Baths
Nitric Oxide Synthase
Neurotransmitter Agents
Glutamic Acid
Nitric Oxide
Immunohistochemistry

Keywords

  • Endothelins
  • Glia
  • Hypothalamus
  • Oxytocin
  • Vasopressin

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity. / Filosa, Jessica Andrea; Naskar, K.; Perfume, G.; Iddings, J. A.; Biancardi, V. C.; Vatta, M. S.; Stern, J. E.

In: Journal of Neuroendocrinology, Vol. 24, No. 2, 01.02.2012, p. 378-392.

Research output: Contribution to journalArticle

Filosa, Jessica Andrea ; Naskar, K. ; Perfume, G. ; Iddings, J. A. ; Biancardi, V. C. ; Vatta, M. S. ; Stern, J. E. / Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity. In: Journal of Neuroendocrinology. 2012 ; Vol. 24, No. 2. pp. 378-392.
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