Higher cognitive functions and complex dynamic tasks performed by the nervous system rely on the tight coordination of brain cells in time and space. In this context, the evolution of complex organisms has resulted in widely varying mechanisms of intercellular communication to ensure proper brain response to external stimuli. In vertebrates, cell-to-cell communication and coordination between neighboring cells are in part mediated by two families of membrane proteins: connexins and pannexins.
Connexins are the protein subunits forming the hexameric ring of a connexon, one half of a gap junction channel (GJC). These “half channels” are usually referred to as "hemichannels" and form a full GJC when they dock with another hemichannel in the apposed membrane of an adjacent cell. GJCs allow for the intercellular exchange of metabolites, second messengers and ions. Given their ubiquitous expression throughout different organs and their ability to allow intercellular communication, connexins are crucial for several physiological functions, including the transmission of intercellular Ca2+ waves, spread of electrotonic potentials, local blood flow regulation and spatial buffering of ions and metabolites. Importantly, hemichannels along with a new family of channels termed pannexons can also serve as single membrane conduits permeable to ions and small molecules, allowing the diffusional exchange between the intra- and extracellular milieu.
In the nervous system, both hemichannels and pannexons permit the release of significant quantities of autocrine/paracrine signaling molecules (e.g., ATP, glutamate, NAD+, adenosine and PGE2) into the extracellular milieu, as well as the uptake of small molecules. An increasing body of evidence has revealed that GJCs, hemichannels and pannexons play a crucial role in a wide-arrange of brain processes including synaptic transmission, blood flow regulation, Ca2+ wave propagation, memory consolidation, neurogenesis, metabolic sensing, migration and adhesion. Because their crucial role in multiple cell signaling functions, the dysfunction of these channels has been proposed to be crucial not only as potential pathological biomarker, but also in the pathogenesis and progression of several neuroinflammatory diseases.
With this Research Topic, we aim to gather a collection of original research articles, short communications, perspectives, as well as review articles, exploring the relationship of connexin- and pannexin-based channels with different aspects of neuroplasticity including but not limited to neurogenesis, regeneration, migration, gliotransmission, neurovascular function, synaptic transmission, learning and memory, sensory systems and behavior. In addition, we will welcome manuscripts providing the latest progress and insights of how connexin- and pannexin-based channels contribute to the pathogenesis and progression of neuroinflammation in different brain diseases. Encompassing studies from animal, clinical, cellular and molecular perspectives, we plan to give a broad overview in the understanding of how gap junctions, hemichannels and pannexons are involved in the physiology and pathophysiology of the nervous system.
Higher cognitive functions and complex dynamic tasks performed by the nervous system rely on the tight coordination of brain cells in time and space. In this context, the evolution of complex organisms has resulted in widely varying mechanisms of intercellular communication to ensure proper brain response to external stimuli. In vertebrates, cell-to-cell communication and coordination between neighboring cells are in part mediated by two families of membrane proteins: connexins and pannexins.
Connexins are the protein subunits forming the hexameric ring of a connexon, one half of a gap junction channel (GJC). These “half channels” are usually referred to as "hemichannels" and form a full GJC when they dock with another hemichannel in the apposed membrane of an adjacent cell. GJCs allow for the intercellular exchange of metabolites, second messengers and ions. Given their ubiquitous expression throughout different organs and their ability to allow intercellular communication, connexins are crucial for several physiological functions, including the transmission of intercellular Ca2+ waves, spread of electrotonic potentials, local blood flow regulation and spatial buffering of ions and metabolites. Importantly, hemichannels along with a new family of channels termed pannexons can also serve as single membrane conduits permeable to ions and small molecules, allowing the diffusional exchange between the intra- and extracellular milieu.
In the nervous system, both hemichannels and pannexons permit the release of significant quantities of autocrine/paracrine signaling molecules (e.g., ATP, glutamate, NAD+, adenosine and PGE2) into the extracellular milieu, as well as the uptake of small molecules. An increasing body of evidence has revealed that GJCs, hemichannels and pannexons play a crucial role in a wide-arrange of brain processes including synaptic transmission, blood flow regulation, Ca2+ wave propagation, memory consolidation, neurogenesis, metabolic sensing, migration and adhesion. Because their crucial role in multiple cell signaling functions, the dysfunction of these channels has been proposed to be crucial not only as potential pathological biomarker, but also in the pathogenesis and progression of several neuroinflammatory diseases.
With this Research Topic, we aim to gather a collection of original research articles, short communications, perspectives, as well as review articles, exploring the relationship of connexin- and pannexin-based channels with different aspects of neuroplasticity including but not limited to neurogenesis, regeneration, migration, gliotransmission, neurovascular function, synaptic transmission, learning and memory, sensory systems and behavior. In addition, we will welcome manuscripts providing the latest progress and insights of how connexin- and pannexin-based channels contribute to the pathogenesis and progression of neuroinflammation in different brain diseases. Encompassing studies from animal, clinical, cellular and molecular perspectives, we plan to give a broad overview in the understanding of how gap junctions, hemichannels and pannexons are involved in the physiology and pathophysiology of the nervous system.
