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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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UNC-7 exhibited hemichannel properties in Neuro2A cells. (A) Representative current traces recorded in UNC-7 non-transfected (n = 11) and transfected (n = 10) Neuro2A cells, respectively. Currents were evoked by step voltage from -120 to +100 mV in increment of 20 mV. Cells were held at -60 mV. (B) Graphic presentation of the average current intensities. Significantly increased currents were observed in UNC-7 transfected Neuro2A cells.
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Figure 7: UNC-7 exhibited hemichannel properties in Neuro2A cells. (A) Representative current traces recorded in UNC-7 non-transfected (n = 11) and transfected (n = 10) Neuro2A cells, respectively. Currents were evoked by step voltage from -120 to +100 mV in increment of 20 mV. Cells were held at -60 mV. (B) Graphic presentation of the average current intensities. Significantly increased currents were observed in UNC-7 transfected Neuro2A cells.

Mentions: We further examined if UNC-7 innexin could exert hemichannel activity when transfected in Neuro2A cells. Indeed, some unpaired UNC-7 transfected Neuro2A cells exhibited current activities upon voltage stimulation (Figure 7A), and the averaged current intensity was significantly increased in UNC-7 transfected Neuro2A cells versus cells transfected with empty vectors (Figure 7B). The same size Neuro2A cells were selected for recording (Control: 26.4 ± 1.9pF, n = 11; +UNC-7: 25.2 ± 1.9pF, n = 10, p > 0.05). Taken together, this result suggests that UNC-7 innexin may exert hemichannel activity when transfected in Neuro2A cells.


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)

UNC-7 exhibited hemichannel properties in Neuro2A cells. (A) Representative current traces recorded in UNC-7 non-transfected (n = 11) and transfected (n = 10) Neuro2A cells, respectively. Currents were evoked by step voltage from -120 to +100 mV in increment of 20 mV. Cells were held at -60 mV. (B) Graphic presentation of the average current intensities. Significantly increased currents were observed in UNC-7 transfected Neuro2A cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: UNC-7 exhibited hemichannel properties in Neuro2A cells. (A) Representative current traces recorded in UNC-7 non-transfected (n = 11) and transfected (n = 10) Neuro2A cells, respectively. Currents were evoked by step voltage from -120 to +100 mV in increment of 20 mV. Cells were held at -60 mV. (B) Graphic presentation of the average current intensities. Significantly increased currents were observed in UNC-7 transfected Neuro2A cells.
Mentions: We further examined if UNC-7 innexin could exert hemichannel activity when transfected in Neuro2A cells. Indeed, some unpaired UNC-7 transfected Neuro2A cells exhibited current activities upon voltage stimulation (Figure 7A), and the averaged current intensity was significantly increased in UNC-7 transfected Neuro2A cells versus cells transfected with empty vectors (Figure 7B). The same size Neuro2A cells were selected for recording (Control: 26.4 ± 1.9pF, n = 11; +UNC-7: 25.2 ± 1.9pF, n = 10, p > 0.05). Taken together, this result suggests that UNC-7 innexin may exert hemichannel activity when transfected in Neuro2A cells.

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