PMID- 28432255 OWN - NLM STAT- MEDLINE DCOM- 20180201 LR - 20210109 IS - 2051-817X (Electronic) IS - 2051-817X (Linking) VI - 5 IP - 8 DP - 2017 Apr TI - Osmotic activation of a Ca(2+)-dependent phospholipase C pathway that regulates ∆N TRPV1-mediated currents in rat supraoptic neurons. LID - 10.14814/phy2.13259 [doi] LID - e13259 AB - The magnocellular neurosecretory cells (MNCs) of the hypothalamus regulate body fluid balance by releasing the hormones vasopressin (VP) and oxytocin (OT) in an osmolality-dependent manner. Elevations of external osmolality increase MNC firing and hormone release. MNC osmosensitivity is largely due to activation of a mechanosensitive non-selective cation current that responds to osmotically-evoked changes in MNC volume and is mediated by an N-terminal variant of the TRPV1 channel (∆N TRPV1). We report a novel mechanism by which increases in osmolality may modulate ∆N TRPV1-mediated currents and thus influence MNC electrical behaviour. We showed previously that acute elevations of external osmolality activate the enzyme phospholipase C (PLC) in isolated MNCs. We now show that the osmotic activation of PLC has a time course and dose-dependence that is consistent with a role in MNC osmosensitivity and that it contributes to the osmotically-evoked increase in non-selective cation current in MNCs through a protein kinase C-dependent pathway. We furthermore show that the mechanism of osmotic activation of PLC requires an increase in internal Ca(2+) that depends on influx through L-type Ca(2+) channels. Our data therefore suggest that MNCs possess an osmotically-activated Ca(2+)-dependent PLC that contributes to the osmotic activation of ∆N TRPV1 and may therefore be important in MNC osmosensitivity and in central osmoregulation. CI - (c) 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. FAU - Bansal, Vimal AU - Bansal V AD - Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. FAU - Fisher, Thomas E AU - Fisher TE AD - Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada thomas.fisher@usask.ca. LA - eng PT - Journal Article PL - United States TA - Physiol Rep JT - Physiological reports JID - 101607800 RN - 0 (Calcium Channels, L-Type) RN - 0 (TRPV Cation Channels) RN - 0 (Trpv1 protein, rat) RN - EC 3.1.4.- (Type C Phospholipases) RN - SY7Q814VUP (Calcium) SB - IM MH - *Action Potentials MH - Animals MH - Calcium/*metabolism MH - Calcium Channels, L-Type/metabolism MH - Cells, Cultured MH - Male MH - Neurons/*metabolism/physiology MH - *Osmotic Pressure MH - Rats MH - Rats, Long-Evans MH - Supraoptic Nucleus/cytology/*metabolism/physiology MH - TRPV Cation Channels/*metabolism MH - Type C Phospholipases/*metabolism PMC - PMC5408288 OTO - NOTNLM OT - Osmosensitivity OT - phospholipase C OT - supraoptic nucleus EDAT- 2017/04/23 06:00 MHDA- 2018/02/02 06:00 PMCR- 2017/04/21 CRDT- 2017/04/23 06:00 PHST- 2017/02/28 00:00 [received] PHST- 2017/03/08 00:00 [accepted] PHST- 2017/04/23 06:00 [entrez] PHST- 2017/04/23 06:00 [pubmed] PHST- 2018/02/02 06:00 [medline] PHST- 2017/04/21 00:00 [pmc-release] AID - 5/8/e13259 [pii] AID - PHY213259 [pii] AID - 10.14814/phy2.13259 [doi] PST - ppublish SO - Physiol Rep. 2017 Apr;5(8):e13259. doi: 10.14814/phy2.13259.