A functional coupling between extrasynaptic NMDA receptors and A-type K+ channels under astrocyte control regulates hypothalamic neurosecretory neuronal activity

Krishna Naskar, Javier Eduardo Stern

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Neuronal activity is controlled by a fine-tuned balance between intrinsic properties and extrinsic synaptic inputs. Moreover, neighbouring astrocytes are now recognized to influence a wide spectrum of neuronal functions. Yet, how these three key factors act in concert to modulate and fine-tune neuronal output is not well understood. Here, we show that in rat hypothalamic magnocellular neurosecretory cells (MNCs), glutamate NMDA receptors (NMDARs) are negatively coupled to the transient, voltage-gated A-type K+ current (IA). We found that activation of NMDARs by extracellular glutamate levels influenced by astrocyte glutamate transporters resulted in a significant inhibition of IA. The NMDAR-IA functional coupling resulted from activation of extrasynaptic NMDARs, was calcium- and protein kinase C-dependent, and involved enhanced steady-state, voltage-dependent inactivation of IA. The NMDAR-IA coupling diminished the latency to the first evoked spike in response to membrane depolarization and increased the total number of evoked action potentials, thus strengthening the neuronal input/output function. Finally, we found a blunted NMDA-mediated inhibition of IA in dehydrated rats. Together, our findings support a novel signalling mechanism that involves a functional coupling between extrasynaptic NMDARs and A-type K+ channels, which is influenced by local astrocytes. We show this signalling complex to play an important role in modulating hypothalamic neuronal excitability, which may contribute to adaptive responses during a sustained osmotic challenge such as dehydration.

Original languageEnglish (US)
Pages (from-to)2813-2827
Number of pages15
JournalJournal of Physiology
Volume592
Issue number13
DOIs
StatePublished - Jul 1 2014

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N-Methyl-D-Aspartate Receptors
Astrocytes
Amino Acid Transport System X-AG
Glutamate Receptors
N-Methylaspartate
Dehydration
Evoked Potentials
Protein Kinase C
Action Potentials
Glutamic Acid
Calcium
Membranes

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)

Cite this

A functional coupling between extrasynaptic NMDA receptors and A-type K+ channels under astrocyte control regulates hypothalamic neurosecretory neuronal activity. / Naskar, Krishna; Stern, Javier Eduardo.

In: Journal of Physiology, Vol. 592, No. 13, 01.07.2014, p. 2813-2827.

Research output: Contribution to journalArticle

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