Synaptic Functions of Hemichannels and Pannexons: A Double-Edged Sword
Date
2018
Type:
Article
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Abstract
The classical view of synapses as the functional contact between presynaptic and
postsynaptic neurons has been challenged in recent years by the emerging regulatory
role of glial cells. Astrocytes, traditionally considered merely supportive elements are
now recognized as active modulators of synaptic transmission and plasticity at the
now so-called “tripartite synapse.” In addition, an increasing body of evidence indicates
that beyond immune functions microglia also participate in various processes aimed to
shape synaptic plasticity. Release of neuroactive compounds of glial origin, -process
known as gliotransmission-, constitute a widespread mechanism through which glial
cells can either potentiate or reduce the synaptic strength. The prevailing vision
states that gliotransmission depends on an intracellular Ca2C/exocytotic-mediated
release; notwithstanding, growing evidence is pointing at hemichannels (connexons) and
pannexin channels (pannexons) as alternative non-vesicular routes for gliotransmitters
efflux. In concurrence with this novel concept, both hemichannels and pannexons are
known to mediate the transfer of ions and signaling molecules -such as ATP and
glutamate- between the cytoplasm and the extracellular milieu. Importantly, recent
reports show that glial hemichannels and pannexons are capable to perceive synaptic
activity and to respond to it through changes in their functional state. In this article,
we will review the current information supporting the “double edge sword” role of
hemichannels and pannexons in the function of central and peripheral synapses. At
one end, available data support the idea that these channels are chief components
of a feedback control mechanism through which gliotransmitters adjust the synaptic
gain in either resting or stimulated conditions. At the other end, we will discuss how
the excitotoxic release of gliotransmitters and [Ca2C] overload linked to the opening of
hemichannels/pannexons might impact cell function and survival in the nervous system
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Citation
Frontiers in Molecular Neuroscience, 2018, 11:435
Keywords
Astrocytes, Microglia, Neuron, LTP, Connexin, Pannexin, Neuroinflammation