title: The Cav3.2 T-type calcium channel regulates temporal coding in mouse mechanoreceptors.
abstract: In mammals there are three types of low-voltage-activated (LVA) calcium channels,Cav3.1, Cav3.2 and Cav3.3, which all give rise to T-type Ca2+currents. T-type Ca2+currents have long been known to be highly enriched in a sub-population of medium-sized sensory neurones in the dorsal root ganglia (DRG). However, the identity of the T-type-rich sensory neurones has remained controversial and the precise physiological role of the Cav3.2 calcium channel in these sensory neurones has not been directly addressed. Here we show, using Cav3.2−/− mutant mice,that these channels are essential for the normal temporal coding of moving stimuli by specialized skin mechanoreceptors called D-hair receptors.We show that D-hair receptors from Cav3.2−/− fire approximately 50% fewer spikes in response to ramp-and-hold displacement stimuli compared to wild type receptors. The reduced sensitivity of D-hair receptors in Cav3.2−/− mice is chiefly due to an increase in the mechanical threshold and a substantial temporal delay in the onset of high-frequency firing to moving stimuli.We examined the receptive properties of other cutaneous mechano receptors and Aδ- and C-fibre nociceptors in Cav3.2−/− mice, but found no alteration in their mechanosensitivity compared to Cav3.2+/+mice. However, C-fibre nociceptors recorded in Cav3.2−/− mutant mice displayed a small but statistically significant reduction in their spiking rate during noxious heat ramps when compared to C-fibres in control mice. The T-type calcium channel Cav3.2 is thus not only a highly specific marker of D-hair receptors but is also required to maintain their high sensitivity and above all to ensure ultra rapid temporal detection of skin movement.
authors.affiliation: Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Berlin-Buch D-13092 Germany.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lewin
mesh_terms: D000200:Action Potentials; D000818:Animals; D020747:Calcium Channels, T-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000378:metabolism; D008465:Mechanoreceptors / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D010812:Physical Stimulation; D011930:Reaction Time; D012684:Sensory Thresholds; D012867:Skin / Q000294:innervation*; D013997:Time Factors
chemical_list: C504883:Cacna1h protein, mouse; D020747:Calcium Channels, T-Type