title: Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons.
abstract: Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca(2+) entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca(2+) buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca(2+)-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca(2+) elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Margas
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK l.ferron@ucl.ac.uk.
authors.forename: Laurent
authors.initials: L
authors.lastname: Ferron
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK.
authors.forename: Manuela
authors.initials: M
authors.lastname: Nieto-Rostro
authors.affiliation: College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0557, USA.
authors.forename: Arnold
authors.initials: A
authors.lastname: Schwartz
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK a.dolphin@ucl.ac.uk.
authors.forename: Annette C
authors.initials: AC
authors.lastname: Dolphin
mesh_terms: D000200:Action Potentials / Q000235:genetics*; D000818:Animals; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000502:physiology*; D008297:Male; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*
chemical_list: D015220:Calcium Channels
keywords: action potential; auxiliary subunit; calcium channel; calcium transient; excitability