PMID- 33707294
OWN - NLM
STAT- MEDLINE
DCOM- 20211119
LR  - 20211119
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 41
IP  - 16
DP  - 2021 Apr 21
TI  - PLCdelta1 Plays Central Roles in the Osmotic Activation of DeltaN-TRPV1 Channels in Mouse 
      Supraoptic Neurons and in Murine Osmoregulation.
PG  - 3579-3587
LID - 10.1523/JNEUROSCI.2892-20.2021 [doi]
AB  - The magnocellular neurosecretory cells (MNCs) of the hypothalamus play a vital 
      role in osmoregulation, but the mechanisms underlying MNC osmosensitivity are not 
      fully understood. We showed previously that high osmolality activates 
      phospholipase C (PLC) in rat MNCs in a Ca(2+)-dependent manner and that PLC 
      activation is necessary for full osmotic activation of an N-terminal variant of 
      the TRPV1 (DeltaN-TRPV1) channel. We therefore hypothesized that the Ca(2+)-dependent 
      delta1 isoform of PLC contributes to DeltaN-TRPV1 activation and tested whether MNC 
      function is defective in a transgenic PLCdelta1 KO mouse. Water deprivation for 24 h 
      caused greater increases in serum osmolality and losses in body weight in PLCdelta1 
      KO mice than it did in control mice. Action potentials and DeltaN-TRPV1 currents were 
      measured in acutely isolated mouse MNCs using whole-cell patch clamp before and 
      after exposure to hypertonic solutions. This treatment elicited a significant 
      activation of DeltaN-TRPV1 currents and an increase in firing rate in MNCs isolated 
      from control mice, but not from PLCdelta1 KO mice. Submembranous filamentous actin 
      was measured in isolated MNCs before and after treatment with angiotensin II and 
      hypertonic solution. Both treatments caused an increase in filamentous actin 
      fluorescence in MNCs isolated from control mice, but both responses were 
      significantly attenuated in MNCs from PLCdelta1 KO mice. Our data demonstrate that 
      the PLCdelta1 isoform plays a key role in the activation of DeltaN-TRPV1 channels and in 
      osmosensory transduction in MNCs. This study advances our understanding of the 
      molecular mechanisms underlying mammalian osmoregulation.SIGNIFICANCE STATEMENT 
      Magnocellular neurosecretory cells (MNCs) of the hypothalamus play a central role 
      in osmoregulation. We have identified a key role for the PLCdelta1 isoform in the 
      activation of DeltaN-TRPV1 channels and osmosensory transduction in MNCs. The data 
      indicate that the PLCdelta1 isoform is activated by the Ca(2+) influx occurring 
      during MNC action potentials and exerts a positive feedback on DeltaN-TRPV1 channels 
      to enhance MNC excitability. This study provides evidence that PLCdelta1 is a key 
      molecule underlying osmosensory transduction, the regulation of VP release, and 
      osmoregulation.
CI  - Copyright (c) 2021 the authors.
FAU - Park, Sung Jin
AU  - Park SJ
AD  - Department of Anatomy, Physiology, and Pharmacology, College of Medicine, 
      University of Saskatchewan, Saskatoon, Saskatchewan Canada S7N 5E5.
FAU - Haan, Kirk D
AU  - Haan KD
AD  - Department of Anatomy, Physiology, and Pharmacology, College of Medicine, 
      University of Saskatchewan, Saskatoon, Saskatchewan Canada S7N 5E5.
FAU - Nakamura, Yoshikazu
AU  - Nakamura Y
AD  - Department of Applied Biological Science, Faculty of Science and Technology, 
      Tokyo University of Science, Noda, Chiba Japan 278-8510.
FAU - Fukami, Kiyoko
AU  - Fukami K
AD  - Laboratory of Genome and Biosignals, School of Life Sciences, Tokyo University of 
      Pharmacy and Life Sciences, Tokyo Japan 192-0392.
FAU - Fisher, Thomas E
AU  - Fisher TE
AD  - Department of Anatomy, Physiology, and Pharmacology, College of Medicine, 
      University of Saskatchewan, Saskatoon, Saskatchewan Canada S7N 5E5 
      thomas.fisher@usask.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210311
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Actins)
RN  - 0 (Hypertonic Solutions)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, mouse)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 3.1.4.11 (Phospholipase C delta)
RN  - EC 3.1.4.11 (Plcd1 protein, mouse)
SB  - IM
MH  - Actins/metabolism
MH  - Action Potentials/physiology
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Electrophysiological Phenomena
MH  - Hypertonic Solutions
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/*metabolism
MH  - Neurosecretory Systems/metabolism
MH  - Osmoregulation/*physiology
MH  - Osmosis
MH  - Phospholipase C delta/genetics/*physiology
MH  - Supraoptic Nucleus/*metabolism
MH  - TRPV Cation Channels/genetics/*metabolism
MH  - Water Deprivation
PMC - PMC8055080
OTO - NOTNLM
OT  - TRPV1
OT  - osmoregulation
OT  - osmosensitivity
OT  - phospholipase C
OT  - supraoptic nucleus
EDAT- 2021/03/13 06:00
MHDA- 2021/11/20 06:00
PMCR- 2021/10/21
CRDT- 2021/03/12 06:27
PHST- 2020/11/13 00:00 [received]
PHST- 2021/02/07 00:00 [revised]
PHST- 2021/03/04 00:00 [accepted]
PHST- 2021/03/13 06:00 [pubmed]
PHST- 2021/11/20 06:00 [medline]
PHST- 2021/03/12 06:27 [entrez]
PHST- 2021/10/21 00:00 [pmc-release]
AID - JNEUROSCI.2892-20.2021 [pii]
AID - JN-RM-2892-20 [pii]
AID - 10.1523/JNEUROSCI.2892-20.2021 [doi]
PST - ppublish
SO  - J Neurosci. 2021 Apr 21;41(16):3579-3587. doi: 10.1523/JNEUROSCI.2892-20.2021. 
      Epub 2021 Mar 11.