Abstract
Major aspects of neuronal function are regulated by Ca2+ including neurotransmitter release, excitability, developmental plasticity, and gene expression. We reported previously that sensory neurons isolated from a mouse model with a heterozygous mutation of the Nf1 gene (Nf1 +/-) exhibited both greater excitability and evoked release of neuropeptides compared to wildtype mice. Furthermore, augmented voltage-dependent sodium currents but not potassium currents contribute to the enhanced excitability. To determine the mechanisms giving rise to the enhanced release of substance P and calcitonin gene-related peptide in the Nf1 +/- sensory neurons, the potential differences in the total voltage-dependent calcium current (ICa) as well as the contributions of individual Ca2+ channel subtypes were assessed. Whole-cell patch-clamp recordings from small-diameter capsaicin-sensitive sensory neurons demonstrated that the average peak ICa densities were not different between the two genotypes. However, by using selective blockers of channel subtypes, the current density of N-type (Cav2.2) ICa was significantly larger in Nf1 +/- neurons compared to wildtype neurons. In contrast, there were no significant differences in L-, P/Q- and R-type currents between the two genotypes. Quantitative real-time polymerase chain reaction measurements made from the isolated but intact dorsal root ganglia indicated that N-type (Cav2.2) and P/Q-type (Cav2.1) Ca2+ channels exhibited the highest mRNA expression levels although there were no significant differences in the levels of mRNA expression between the genotypes. These results suggest that the augmented N-type (Cav2.2) ICa observed in the Nf1 +/- sensory neurons does not result from genomic differences but may reflect post-translational or some other non-genomic modifications. Thus, our results demonstrate that sensory neurons from Nf1 +/- mice, exhibit increased N-type ICa and likely account for the increased release of substance P and calcitonin gene-related peptide that occurs in Nf1 +/- sensory neurons.
| Original language | English |
|---|---|
| Pages (from-to) | 192-202 |
| Number of pages | 11 |
| Journal | Neuroscience |
| Volume | 270 |
| DOIs | |
| State | Published - Jun 13 2014 |
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Keywords
- Calcium channels
- Dorsal root ganglia
- MRNA
- Neurofibromatosis
- QPCR
ASJC Scopus subject areas
- Neuroscience(all)
- Medicine(all)
Cite this
N-type calcium current, Cav2.2, is enhanced in small-diameter sensory neurons isolated from Nf1 +/- mice. / Duan, J. H.; Hodgdon, K. E.; Hingtgen, C. M.; Nicol, Grant.
In: Neuroscience, Vol. 270, 13.06.2014, p. 192-202.Research output: Contribution to journal › Article
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TY - JOUR
T1 - N-type calcium current, Cav2.2, is enhanced in small-diameter sensory neurons isolated from Nf1 +/- mice
AU - Duan, J. H.
AU - Hodgdon, K. E.
AU - Hingtgen, C. M.
AU - Nicol, Grant
PY - 2014/6/13
Y1 - 2014/6/13
N2 - Major aspects of neuronal function are regulated by Ca2+ including neurotransmitter release, excitability, developmental plasticity, and gene expression. We reported previously that sensory neurons isolated from a mouse model with a heterozygous mutation of the Nf1 gene (Nf1 +/-) exhibited both greater excitability and evoked release of neuropeptides compared to wildtype mice. Furthermore, augmented voltage-dependent sodium currents but not potassium currents contribute to the enhanced excitability. To determine the mechanisms giving rise to the enhanced release of substance P and calcitonin gene-related peptide in the Nf1 +/- sensory neurons, the potential differences in the total voltage-dependent calcium current (ICa) as well as the contributions of individual Ca2+ channel subtypes were assessed. Whole-cell patch-clamp recordings from small-diameter capsaicin-sensitive sensory neurons demonstrated that the average peak ICa densities were not different between the two genotypes. However, by using selective blockers of channel subtypes, the current density of N-type (Cav2.2) ICa was significantly larger in Nf1 +/- neurons compared to wildtype neurons. In contrast, there were no significant differences in L-, P/Q- and R-type currents between the two genotypes. Quantitative real-time polymerase chain reaction measurements made from the isolated but intact dorsal root ganglia indicated that N-type (Cav2.2) and P/Q-type (Cav2.1) Ca2+ channels exhibited the highest mRNA expression levels although there were no significant differences in the levels of mRNA expression between the genotypes. These results suggest that the augmented N-type (Cav2.2) ICa observed in the Nf1 +/- sensory neurons does not result from genomic differences but may reflect post-translational or some other non-genomic modifications. Thus, our results demonstrate that sensory neurons from Nf1 +/- mice, exhibit increased N-type ICa and likely account for the increased release of substance P and calcitonin gene-related peptide that occurs in Nf1 +/- sensory neurons.
AB - Major aspects of neuronal function are regulated by Ca2+ including neurotransmitter release, excitability, developmental plasticity, and gene expression. We reported previously that sensory neurons isolated from a mouse model with a heterozygous mutation of the Nf1 gene (Nf1 +/-) exhibited both greater excitability and evoked release of neuropeptides compared to wildtype mice. Furthermore, augmented voltage-dependent sodium currents but not potassium currents contribute to the enhanced excitability. To determine the mechanisms giving rise to the enhanced release of substance P and calcitonin gene-related peptide in the Nf1 +/- sensory neurons, the potential differences in the total voltage-dependent calcium current (ICa) as well as the contributions of individual Ca2+ channel subtypes were assessed. Whole-cell patch-clamp recordings from small-diameter capsaicin-sensitive sensory neurons demonstrated that the average peak ICa densities were not different between the two genotypes. However, by using selective blockers of channel subtypes, the current density of N-type (Cav2.2) ICa was significantly larger in Nf1 +/- neurons compared to wildtype neurons. In contrast, there were no significant differences in L-, P/Q- and R-type currents between the two genotypes. Quantitative real-time polymerase chain reaction measurements made from the isolated but intact dorsal root ganglia indicated that N-type (Cav2.2) and P/Q-type (Cav2.1) Ca2+ channels exhibited the highest mRNA expression levels although there were no significant differences in the levels of mRNA expression between the genotypes. These results suggest that the augmented N-type (Cav2.2) ICa observed in the Nf1 +/- sensory neurons does not result from genomic differences but may reflect post-translational or some other non-genomic modifications. Thus, our results demonstrate that sensory neurons from Nf1 +/- mice, exhibit increased N-type ICa and likely account for the increased release of substance P and calcitonin gene-related peptide that occurs in Nf1 +/- sensory neurons.
KW - Calcium channels
KW - Dorsal root ganglia
KW - MRNA
KW - Neurofibromatosis
KW - QPCR
UR - http://www.scopus.com/inward/record.url?scp=84899838246&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899838246&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2014.04.021
DO - 10.1016/j.neuroscience.2014.04.021
M3 - Article
C2 - 24755485
AN - SCOPUS:84899838246
VL - 270
SP - 192
EP - 202
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
ER -