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Inorganic polyphosphate regulates neuronal excitability through modulation of voltage-gated channels
Stephanie C Stotz, Lucas Om Scott, Christopher Drummond-Main
1Department of Physiology & Pharmacology and the Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada. mcolicos@ucalgary.ca.
Molecular Brain
|June 3, 2014
Summary
Inorganic polyphosphate (polyP) acts as an excitatory neuromodulator. Neurons release polyP, which modulates ion channels to increase neuronal firing in both the central and peripheral nervous systems.
Area of Science:
- Neuroscience
- Molecular Biology
- Cellular Signaling
Background:
- Inorganic polyphosphate (polyP) is a charged polyanion involved in extracellular signaling.
- While polyP release by astrocytes and platelets is known, its role in neuronal activity was undefined.
- This study investigates polyP's function in neuronal signaling and its molecular mechanisms.
Purpose of the Study:
- To determine if neurons release polyP.
- To investigate polyP's effect on neuronal firing.
- To elucidate the molecular mechanisms of polyP's action on voltage-gated channels.
Main Methods:
- Patch clamp electrophysiology on primary hippocampal and dorsal root ganglion neurons.
- Calcium imaging of neuronal networks and glial cells.
- In situ DAPI localization and live imaging.
- Biochemical assays on synaptosomes.
Main Results:
- PolyP directly induces action potential generation in CNS and PNS neurons.
- PolyP modulates NaV, KV, and CaV channels, increasing neuronal excitability.
- PolyP enhances neuronal network activity and induces calcium influx in glial cells.
- PolyP is present in synapses and released from neurons upon depolarization.
Conclusions:
- PolyP release increases neuronal membrane excitability by modulating voltage-gated ion channels.
- PolyP functions as an excitatory neuromodulator in both the peripheral and central nervous systems.
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