Pain perception in mice lacking the β3 subunit of voltage-activated calcium channels

Abstract

The importance of voltage-activated calcium channels in pain processing has been suggested by the spinal antinociceptive action of blockers of N- and P/Q-type calcium channels as well as by gene targeting of the α1B subunit (N-type). The accessory β3 subunits of calcium channels are preferentially associated with the a1β subunit in neurones. Here we show that deletion of the β3 subunit by gene targeting affects strongly the pain processing of mutant mice. We pinpoint this defect in the pain-related behavior and ascending pain pathways of the spinal cord in vivo and at the level of calcium channel currents and proteins in single dorsal root ganglion neurones in vitro. The pain induced by chemical inflammation is preferentially damped by deletion of β3 sub-units, whereas responses to acute thermal and mechanical harmful stimuli are reduced moderately or not at all, respectively. The defect results in a weak wind-up of spinal cord activity during intense afferent nerve stimulation. The molecular mechanism responsible for the phenotype was traced to low expression of N-type calcium channels (α1B) and functional alterations of calcium channel currents in neurones projecting to the spinal cord.