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- Title
A Closely Associated Phospholipase C Regulates Cation Channel Function through Phosphoinositide Hydrolysis.
- Authors
Sturgeon, Raymond M.; Magoski, Neil S.
- Abstract
In the hemaphroditic sea snail, Aplysia californica, reproduction is initiated when the bag cell neurons secrete egg-laying hormone during a protracted afterdischarge. A source of depolarization for the afterdischarge is a voltage-gated, nonselective cation channel, similar to transient receptor potential (TRP) channels. Once the afterdischarge is triggered, phospholipase C (PLC) is activated to hydrolyze phosphatidylinositol- 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3). We previously reported that a DAG analog, 1-oleoyl-2-acetyl-sn-glycerol (OAG), activates a prominent, inward whole-cell cationic current that is enhanced by IP3. To examine the underlying mechanism, we investigated the effect of exogenous OAG and IP3, as well as PLC activation, on cation channel activity and voltage dependence in excised, inside-out patches from cultured bag cell neurons. OAG transiently elevated channel open probability (Po) when applied to excised patches; however, coapplication of IP3 prolonged the OAG-induced response. In patches exposed to OAG and IP3, channel voltage dependence was left-shifted; this was also observed with OAG, but not to the same extent. Introducing the PLC activator, m-3M3FBS, to patches increased channel Po, suggesting PLC may be physically linked to the channels. Accordingly, blocking PLC with U-73122 ablated the m-3M3FBS-induced elevation in Po. Treatment with m-3M3FBS left-shifted cation channel voltage dependence to a greater extent than exogenous OAG and IP3. Finally, OAG and IP3 potentiated the stimulatory effect of PKC, which is also associated with the channel. Thus, the PLC-PKC signaling system is physically localized such that PIP2 breakdown products liberated during the afterdischarge modulate the cation channel and temporally influence neuronal activity.
- Subjects
APLYSIA californica; NEURONS; HORMONES; INOSITOL trisphosphate; DIGLYCERIDES
- Publication
Journal of Neuroscience, 2018, Vol 38, Issue 35, p7622
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0586-18.2018