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      Pannexins, a family of gap junction proteins expressed in brain

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      Proceedings of the National Academy of Sciences
      Proceedings of the National Academy of Sciences

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          Abstract

          Database search has led to the identification of a family of proteins, the pannexins, which share some structural features with the gap junction forming proteins of invertebrates and vertebrates. The function of these proteins has remained unclear so far. To test the possibility that pannexins underlie electrical communication in the brain, we have investigated their tissue distribution and functional properties. Here, we show that two of these genes, pannexin 1 (Px1) and Px2, are abundantly expressed in the CNS. In many neuronal cell populations, including hippocampus, olfactory bulb, cortex and cerebellum, there is coexpression of both pannexins, whereas in other brain regions, e.g., white matter, only Px1-positive cells were found. On expression in Xenopus oocytes, Px1, but not Px2 forms functional hemichannels. Coinjection of both pannexin RNAs results in hemichannels with functional properties that are different from those formed by Px1 only. In paired oocytes, Px1, alone and in combination with Px2, induces the formation of intercellular channels. The functional characteristics of homomeric Px1 versus heteromeric Px1/Px2 channels and the different expression patterns of Px1 and Px2 in the brain indicate that pannexins form cell type-specific gap junctions with distinct properties that may subserve different functions.

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          Most cited references32

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          Two networks of electrically coupled inhibitory neurons in neocortex.

          Inhibitory interneurons are critical to sensory transformations, plasticity and synchronous activity in the neocortex. There are many types of inhibitory neurons, but their synaptic organization is poorly understood. Here we describe two functionally distinct inhibitory networks comprising either fast-spiking (FS) or low-threshold spiking (LTS) neurons. Paired-cell recordings showed that inhibitory neurons of the same type were strongly interconnected by electrical synapses, but electrical synapses between different inhibitory cell types were rare. The electrical synapses were strong enough to synchronize spikes in coupled interneurons. Inhibitory chemical synapses were also common between FS cells, and between FS and LTS cells, but LTS cells rarely inhibited one another. Thalamocortical synapses, which convey sensory information to the cortex, specifically and strongly excited only the FS cell network. The electrical and chemical synaptic connections of different types of inhibitory neurons are specific, and may allow each inhibitory network to function independently.
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            Structural and functional diversity of connexin genes in the mouse and human genome.

            Gap junctions are clustered channels between contacting cells through which direct intercellular communication via diffusion of ions and metabolites can occur. Two hemichannels, each built up of six connexin protein subunits in the plasma membrane of adjacent cells, can dock to each other to form conduits between cells. We have recently screened mouse and human genomic data bases and have found 19 connexin (Cx) genes in the mouse genome and 20 connexin genes in the human genome. One mouse connexin gene and two human connexin genes do not appear to have orthologs in the other genome. With three exceptions, the characterized connexin genes comprise two exons whereby the complete reading frame is located on the second exon. Targeted ablation of eleven mouse connexin genes revealed basic insights into the functional diversity of the connexin gene family. In addition, the phenotypes of human genetic disorders caused by mutated connexin genes further complement our understanding of connexin functions in the human organism. In this review we compare currently identified connexin genes in both the mouse and human genome and discuss the functions of gap junctions deduced from targeted mouse mutants and human genetic disorders.
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              A network of fast-spiking cells in the neocortex connected by electrical synapses.

              Encoding of information in the cortex is thought to depend on synchronous firing of cortical neurons. Inhibitory neurons are known to be critical in the coordination of cortical activity, but how interaction among inhibitory cells promotes synchrony is not well understood. To address this issue directly, we have recorded simultaneously from pairs of fast-spiking (FS) cells, a type of gamma-aminobutyric acid (GABA)-containing neocortical interneuron. Here we report a high occurrence of electrical coupling among FS cells. Electrical synapses were not found among pyramidal neurons or between FS cells and other cortical cells. Some FS cells were interconnected by both electrical and GABAergic synapses. We show that communication through electrical synapses allows excitatory signalling among inhibitory cells and promotes their synchronous spiking. These results indicate that electrical synapses establish a network of fast-spiking cells in the neocortex which may play a key role in coordinating cortical activity.
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                Author and article information

                Journal
                Proceedings of the National Academy of Sciences
                Proceedings of the National Academy of Sciences
                Proceedings of the National Academy of Sciences
                0027-8424
                1091-6490
                May 01 2011
                November 11 2003
                November 03 2003
                November 11 2003
                : 100
                : 23
                : 13644-13649
                Article
                10.1073/pnas.2233464100
                263867
                14597722
                f46d01cf-c4ee-4d0b-b92b-5887c655f75d
                © 2003
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