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A co-operative regulation of neuronal excitability by UNC-7 innexin and NCA/NALCN leak channel.

Bouhours M, Po MD, Gao S, Hung W, Li H, Georgiou J, Roder JC, Zhen M - Mol Brain (2011)

Bottom Line: While the loss of the neuronal NCA channel function leads to a reduced evoked postsynaptic current at neuromuscular junctions, a simultaneous loss of the UNC-7 function restores the evoked response.The expression of UNC-7 in neurons reverts the effect of the unc-7 mutation; moreover, the expression of UNC-7 mutant proteins that are predicted to be unable to form gap junctions also reverts this effect, suggesting that UNC-7 innexin regulates neuronal activity, in part, through gap junction-independent functions.We propose that, in addition to gap junction-mediated functions, UNC-7 innexin may also form hemichannels to regulate C. elegans' neuronal activity cooperatively with the NCA family leak channels.

View Article: PubMed Central - HTML - PubMed

Affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada M5G 1X5.

ABSTRACT
Gap junctions mediate the electrical coupling and intercellular communication between neighboring cells. Some gap junction proteins, namely connexins and pannexins in vertebrates, and innexins in invertebrates, may also function as hemichannels. A conserved NCA/Dmα1U/NALCN family cation leak channel regulates the excitability and activity of vertebrate and invertebrate neurons. In the present study, we describe a genetic and functional interaction between the innexin UNC-7 and the cation leak channel NCA in Caenorhabditis elegans neurons. While the loss of the neuronal NCA channel function leads to a reduced evoked postsynaptic current at neuromuscular junctions, a simultaneous loss of the UNC-7 function restores the evoked response. The expression of UNC-7 in neurons reverts the effect of the unc-7 mutation; moreover, the expression of UNC-7 mutant proteins that are predicted to be unable to form gap junctions also reverts this effect, suggesting that UNC-7 innexin regulates neuronal activity, in part, through gap junction-independent functions. We propose that, in addition to gap junction-mediated functions, UNC-7 innexin may also form hemichannels to regulate C. elegans' neuronal activity cooperatively with the NCA family leak channels.

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Tissue specificity of UNC-7 expression for aldicarb phenotype. unc-7(hp121) animals expressing UNC-7 by pan-neuronal (Prgef-1), cholinergic (Pacr-2) and interneuron (Pglr-1) promoters were assayed for aldicarb sensitivity. Representative results of a same-day experiment on the percentage of mobile animals after 240 minutes of aldicarb exposure at indicated concentrations (see Methods, n = 10 animals per strain). Pan-neuronally expressed UNC-7 rescued aldicarb sensitivity, but expression of UNC-7 in cholinergic or interneurons failed to rescue aldicarb sensitivity.
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Figure 2: Tissue specificity of UNC-7 expression for aldicarb phenotype. unc-7(hp121) animals expressing UNC-7 by pan-neuronal (Prgef-1), cholinergic (Pacr-2) and interneuron (Pglr-1) promoters were assayed for aldicarb sensitivity. Representative results of a same-day experiment on the percentage of mobile animals after 240 minutes of aldicarb exposure at indicated concentrations (see Methods, n = 10 animals per strain). Pan-neuronally expressed UNC-7 rescued aldicarb sensitivity, but expression of UNC-7 in cholinergic or interneurons failed to rescue aldicarb sensitivity.

Mentions: Taken together, these results indicate that the locomotion phenotype, pharmacological response, as well as synaptic morphological defects of unc-7 mutants are unlikely to result from a simple deficit in synaptic transmission at NMJs. Indeed, the strong resistance to aldicarb, a cholinesterase inhibitor that perturbs cholinergic synaptic transmission, exhibited by unc-7 mutants, could only be consistently restored by pan-neuronal expression of UNC-7 ([42]; Figure 2). The altered pharmacological response of unc-7 mutants may result from multiple neuronal types, or a cell type not tested.


A co-operative regulation of neuronal excitability by UNC-7 innexin and NCA/NALCN leak channel.

Bouhours M, Po MD, Gao S, Hung W, Li H, Georgiou J, Roder JC, Zhen M - Mol Brain (2011)

Tissue specificity of UNC-7 expression for aldicarb phenotype. unc-7(hp121) animals expressing UNC-7 by pan-neuronal (Prgef-1), cholinergic (Pacr-2) and interneuron (Pglr-1) promoters were assayed for aldicarb sensitivity. Representative results of a same-day experiment on the percentage of mobile animals after 240 minutes of aldicarb exposure at indicated concentrations (see Methods, n = 10 animals per strain). Pan-neuronally expressed UNC-7 rescued aldicarb sensitivity, but expression of UNC-7 in cholinergic or interneurons failed to rescue aldicarb sensitivity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3102621&req=5

Figure 2: Tissue specificity of UNC-7 expression for aldicarb phenotype. unc-7(hp121) animals expressing UNC-7 by pan-neuronal (Prgef-1), cholinergic (Pacr-2) and interneuron (Pglr-1) promoters were assayed for aldicarb sensitivity. Representative results of a same-day experiment on the percentage of mobile animals after 240 minutes of aldicarb exposure at indicated concentrations (see Methods, n = 10 animals per strain). Pan-neuronally expressed UNC-7 rescued aldicarb sensitivity, but expression of UNC-7 in cholinergic or interneurons failed to rescue aldicarb sensitivity.
Mentions: Taken together, these results indicate that the locomotion phenotype, pharmacological response, as well as synaptic morphological defects of unc-7 mutants are unlikely to result from a simple deficit in synaptic transmission at NMJs. Indeed, the strong resistance to aldicarb, a cholinesterase inhibitor that perturbs cholinergic synaptic transmission, exhibited by unc-7 mutants, could only be consistently restored by pan-neuronal expression of UNC-7 ([42]; Figure 2). The altered pharmacological response of unc-7 mutants may result from multiple neuronal types, or a cell type not tested.

Bottom Line: While the loss of the neuronal NCA channel function leads to a reduced evoked postsynaptic current at neuromuscular junctions, a simultaneous loss of the UNC-7 function restores the evoked response.The expression of UNC-7 in neurons reverts the effect of the unc-7 mutation; moreover, the expression of UNC-7 mutant proteins that are predicted to be unable to form gap junctions also reverts this effect, suggesting that UNC-7 innexin regulates neuronal activity, in part, through gap junction-independent functions.We propose that, in addition to gap junction-mediated functions, UNC-7 innexin may also form hemichannels to regulate C. elegans' neuronal activity cooperatively with the NCA family leak channels.

View Article: PubMed Central - HTML - PubMed

Affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada M5G 1X5.

ABSTRACT
Gap junctions mediate the electrical coupling and intercellular communication between neighboring cells. Some gap junction proteins, namely connexins and pannexins in vertebrates, and innexins in invertebrates, may also function as hemichannels. A conserved NCA/Dmα1U/NALCN family cation leak channel regulates the excitability and activity of vertebrate and invertebrate neurons. In the present study, we describe a genetic and functional interaction between the innexin UNC-7 and the cation leak channel NCA in Caenorhabditis elegans neurons. While the loss of the neuronal NCA channel function leads to a reduced evoked postsynaptic current at neuromuscular junctions, a simultaneous loss of the UNC-7 function restores the evoked response. The expression of UNC-7 in neurons reverts the effect of the unc-7 mutation; moreover, the expression of UNC-7 mutant proteins that are predicted to be unable to form gap junctions also reverts this effect, suggesting that UNC-7 innexin regulates neuronal activity, in part, through gap junction-independent functions. We propose that, in addition to gap junction-mediated functions, UNC-7 innexin may also form hemichannels to regulate C. elegans' neuronal activity cooperatively with the NCA family leak channels.

Show MeSH
Related in: MedlinePlus