Gene deletion of the voltage-gated calcium channel auxiliary subunit α
2
δ-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 α
2
δ-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 α
2
δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α
2
δ-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 α
2
δ-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 α
2
δ-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 α
2
δ-1 knockout sensory neurons.
This article is part of the themed issue ‘Evolution brings Ca
2+
and ATP together to control life and death’.
Analgesic α-conotoxins Vc1.1 and Rg1A inhibit N-type calcium channels in sensory neurons of α9 nicotinic receptor knockout mice