PMID- 24835172
OWN - NLM
STAT- MEDLINE
DCOM- 20150221
LR  - 20211021
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 592
IP  - 13
DP  - 2014 Jul 1
TI  - A functional coupling between extrasynaptic NMDA receptors and A-type K+ channels 
      under astrocyte control regulates hypothalamic neurosecretory neuronal activity.
PG  - 2813-27
LID - 10.1113/jphysiol.2014.270793 [doi]
AB  - 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.
CI  - (c) 2014 The Authors. The Journal of Physiology (c) 2014 The Physiological Society.
FAU - Naskar, Krishna
AU  - Naskar K
AD  - Department of Physiology, Medical College of Georgia, Georgia Regents University, 
      Augusta, GA, 30912, USA.
FAU - Stern, Javier E
AU  - Stern JE
AD  - Department of Physiology, Medical College of Georgia, Georgia Regents University, 
      Augusta, GA, 30912, USA jstern@gru.edu.
LA  - eng
GR  - R01 HL112225/HL/NHLBI NIH HHS/United States
GR  - HL112225/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140516
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Action Potentials
MH  - Animals
MH  - Astrocytes/drug effects/*metabolism/physiology
MH  - Calcium/metabolism
MH  - Glutamic Acid/pharmacology
MH  - Hypothalamus/cytology/*metabolism/physiology
MH  - Male
MH  - Neurons/*metabolism/physiology
MH  - Neurosecretory Systems/cytology/*metabolism/physiology
MH  - Osmotic Pressure
MH  - Potassium Channels, Voltage-Gated/*metabolism
MH  - Protein Kinase C/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reaction Time
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Synapses/*metabolism/physiology
PMC - PMC4221822
EDAT- 2014/05/20 06:00
MHDA- 2015/02/24 06:00
PMCR- 2015/07/01
CRDT- 2014/05/20 06:00
PHST- 2014/05/20 06:00 [entrez]
PHST- 2014/05/20 06:00 [pubmed]
PHST- 2015/02/24 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - jphysiol.2014.270793 [pii]
AID - 10.1113/jphysiol.2014.270793 [doi]
PST - ppublish
SO  - J Physiol. 2014 Jul 1;592(13):2813-27. doi: 10.1113/jphysiol.2014.270793. Epub 
      2014 May 16.