Signalling properties of inorganic polyphosphate in the mammalian brain

• Published in: Nature communications 2013-01, Vol.4 (1), p.1362-1362, Article 1362
• Main Authors: Holmström, Kira M., Marina, Nephtali, Baev, Artyom Y., Wood, Nicholas W., Gourine, Alexander V., Abramov, Andrey Y.
• Format: Article
• Language: English
• Subjects: 631/378/1697; 631/378/2596/1308; 631/80/86; Animals; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - metabolism; Blood pressure; Brain; Brain - drug effects; Brain - metabolism; Brain Stem - drug effects; Brain Stem - physiology; Calcium - pharmacology; Calcium Signaling - drug effects; Cells, Cultured; Coculture Techniques; Enzymes; Heart - drug effects; Heart - physiology; Humanities and Social Sciences; Male; Mammals - metabolism; multidisciplinary; Neurosciences; Polyphosphates - metabolism; Polyphosphates - pharmacology; Polyps; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2Y1 - metabolism; Respiration - drug effects; Science; Science (multidisciplinary); Signal Transduction - drug effects
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms2364

Inorganic polyphosphate is known to be present in the mammalian brain at micromolar concentrations. Here we show that polyphosphate may act as a gliotransmitter, mediating communication between astrocytes. It is released by astrocytes in a calcium-dependent manner and signals to neighbouring astrocytes through P2Y 1 purinergic receptors, activation of phospholipase C and release of calcium from the intracellular stores. In primary neuroglial cultures, application of polyP triggers release of endogenous polyphosphate from astrocytes while neurons take it up. In vivo , central actions of polyphosphate at the level of the brainstem include profound increases in key homeostatic physiological activities, such as breathing, central sympathetic outflow and the arterial blood pressure. Together, these results suggest a role for polyphosphate as a mediator of astroglial signal transmission in the mammalian brain. Inorganic polyphosphates have been identified in the central nervous system. Holmström and colleagues examine neuroglial cultures in vitro and cardiorespiratory responses in vivo , and find that inorganic polyphosphates trigger calcium-dependent activation of astrocytes and increase cardiorespiratory activity.