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: Wojciech Margas, Laurent Ferron, Manuela Nieto-Rostro, Arnold Schwartz, Annette C Dolphin
• Journal: Philosophical transactions of the Royal Society of London. Series B, Biological sciences (Philos Trans R Soc Lond B Biol Sci) Vol. 371 Issue 1700 (08 05 2016) ISSN: 1471-2970 [Electronic] England
• PMID: 27377724 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 The Authors.

Chemical References

• Calcium Channels

Topics

• Action Potentials (genetics)
• Animals
• Calcium Channels (genetics, metabolism)
• Female
• Ganglia, Spinal (physiology)
• Male
• Mice, Knockout
• Neurons (physiology)