Mice mechanoreceptors are modulated by Cav3.2 T‐type calcium channels

Abstract

Mechanoreceptors are sensory receptors that respond to mechanical displacement and provide the senses of touch, pressure, vibration and proprioception. Mice have three types of low-threshold mechanoreceptors: slowly adapting mechanoreceptors (SAMs), rapidly adapting mechanoreceptors (RAMs) and D-hair receptors (Driscoll & Tavernarakis, 2000). D-hair receptors are the end-terminal of type Aδ fibre axons and present a high sensitivity and ultra-rapid temporal detection of slowly moving stimuli. The mRNA expression for the T-type voltage-gated calcium channel Cav3.2 is the only marker defined for mechanoreceptors and found almost exclusively in D-hair receptors. The Cav3.2 gene encodes one of the three low-voltage-activated (LVA) Ca2+ channels (Cav3.1, Cav3.2 and Cav3.3) and are all expressed by sensory neurons in the DRG (Iftinca et al. 2007). Previous published studies proposed that Cav3.2 channel has a primary role in nociception (Bourinet et al. 2005). However, another research group that used miberfradil, a drug that blocks all T-type channels, suggested that the mechanosensitivity of D-hair receptors is reduced by blockade of LVA channels (Shin et al. 2003). For this reason the specific physiological properties of the Cav3.2 channel has not been accurately described. In a recent issue of The Journal of Physiology, Wang & Lewin (2011) conducted a study with the purpose of demonstrating the role of the T-type Cav3.2 channels. In this study, Cav3.2−/− mutant mice were used to directly address the role of this channel in sensory transduction of cutaneous mechanoreceptors and nociceptors. Mice were produced by gene targeting in mouse ES cells; the targeting vector was designed to delete the IS5 region of the murine Cacna1H gene, which resulted in deletion of exon 6, corresponding to amino acid residues 216 to 267. This method was helpful in examining the mechanosensitivity of nociceptors and mechanoreceptors in normal Cav3.2 mice and in Cav3.2−/− mutant mice, proving that nociceptors sensitivity was not altered when the Cav3.2 gene was suppressed; on the other hand, D-hair receptor sensibility was drastically impaired in their ability to encode the properties of moving stimuli, losing their high sensitivity and ability to ensure rapid temporal detection to skin movement. In addition the functional properties of other mechanoreceptors and nociceptors were unaffected by the suppression of Cav3.2 channels. Why is this important? These new data provide conclusive results of the specific function of the T-type Cav3.2 channel, solving the previous controversy about its physiological function and proving that this specific gene is responsible for providing the functional and distinctive properties of D-hair receptors. Thus, this study encloses the specific activity of this gene, being now considered not only a high specific marker of D-hair receptors but also indispensable to maintain their high sensitivity in the detection of skin deflection. The expression of Cav3.2 in D-hair mechanoreceptors may serve to provide highly accurate temporal information about rapidly changing stimuli. This information helps humans to make fast and precise judgments about the speed and direction of tactile stimuli, a characteristic that can be considered vital for survival and functionality. This is the first time that the regulation for temporal coding in mouse mechanoreceptors from Cav3.2 T-type channels has been proved. Nevertheless, results from this study showed that there exists a possibility that a minor sub-population of nociceptors is dependent on the presence of Cav3.2 channels. The research revealed no certainty that such a population exists, and it is highly unlikely that this kind of population could be identified. Further studies will be needed to ascertain if this is indeed a possibility.