title: N-type calcium current, Cav2.2, is enhanced in small-diameter sensory neurons isolated from Nf1+/- mice.
abstract: Major aspects of neuronal function are regulated by Ca(2+) 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 Ca(2+) 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) Ca(2+) 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.
authors.affiliation: Department of Pharmacology & Toxicology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: J-H
authors.initials: JH
authors.lastname: Duan
authors.affiliation: Department of Pharmacology & Toxicology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Hodgdon
authors.affiliation: Department of Pharmacology & Toxicology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA; Department of Neurology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Hingtgen
authors.affiliation: Department of Pharmacology & Toxicology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA. Electronic address: gnicol@iupui.edu.
authors.forename: G D
authors.initials: GD
authors.lastname: Nicol
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D018689:Sensory System Agents / Q000494:pharmacology
chemical_list: C514350:CACNA1C protein, mouse; C500963:Cacna1b protein, mouse; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D025542:Neurofibromin 1; D012333:RNA, Messenger; D018689:Sensory System Agents; D002211:Capsaicin; D002118:Calcium
keywords: calcium channels; dorsal root ganglia; mRNA; neurofibromatosis; qPCR
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