The mammalian sodium channel BNC1 is required for normal touch sensation

Abstract

Of the vertebrate senses, touch is the least understood at the molecular level The ion channels that form the core of the mechanosensory complex and confer touch sensitivity remain unknown. However, the similarity of the brain sodium channel 1 (BNC1) to nematode proteins involved in mechanotransduction indicated that it might be a part of such a mechanosensor. Here we show that disrupting the mouse BNC1 gene markedly reduces the sensitivity of a specific component of mechanosensation: low-threshold rapidly adapting mechanoreceptors. In rodent hairy skin these mechanoreceptors are excited by hair movement. Consistent with this function, we found BNC1 in the lanceolate nerve endings that lie adjacent to and surround the hair follicle. Although BNC1 has been proposed to have a role in pH sensing, the acid-evoked current in cultured sensory neurons and the response of acid-stimulated nociceptors were normal in BNC1 null mice. These data identify the BNC1 channel as essential for the normal detection of light touch and indicate that BNC1 may be a central component of a mechanosensory complex.

DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature

“…Dorsal Root Ganglia (DRG) Neuron Electrophysiology. Mouse DRG neurons were cultured from C57BL͞6 mice as described (7,25). Cells were incubated overnight at room temperature or at 37°C.…”

“…In Caenorhabditis elegans, the DEG͞ENaC channel subunits MEC-4 and MEC-10 are expressed in touch cell neurons, where they are thought to form part of the mechanoreceptor complex (3). In mammals, the DEG͞ENaC channel BNC1 (4) [also called MDEG (5), BNaC1 (6), and ASIC2 (2)] is expressed in lanceolate nerve endings at the site of mechanotransduction (7). Targeted disruption of the BNC1 gene in mice reduced the sensitivity of low-threshold, rapidly adapting mechanoreceptors, indicating that BNC1 is required for normal touch sensation (7).…”

“…In mammals, the DEG͞ENaC channel BNC1 (4) [also called MDEG (5), BNaC1 (6), and ASIC2 (2)] is expressed in lanceolate nerve endings at the site of mechanotransduction (7). Targeted disruption of the BNC1 gene in mice reduced the sensitivity of low-threshold, rapidly adapting mechanoreceptors, indicating that BNC1 is required for normal touch sensation (7). The related channel subunits ASIC (8) [also called BNaC2 (6) and ASIC1 (2)] and DRASIC (9) [also called ASIC3 (2)] are also expressed in peripheral sensory neurons; because they are activated by acidic pH, it has been proposed that they play a role in nociception (2).…”

The acid-sensing ion channel 2 (ASIC2) of ciliated cells in the developing rat nasal septum

“…A study of ASIC2 null mice showed that ASIC2 was a central component of a mechanosensory complex (Price et al, 2000). However, a study of ASIC2 gene knockout in the mouse suggested that ASIC2 was not part of a mechanically gated cation channel important for cutaneous mechanosensation, Summary.…”

“…Previous studies revealed that ASICs are involved in a wide range of neuronal functions such as synaptic plasticity (Wemmie et al 2003), mechanosensation (Price et al 2000;, nociception linked to local tissue acidosis, sour-taste reception (Ugawa et al 1998), and the modulation of retinal and cochlear functions (Ettaiche et al 2004). It is also known that ASICs respond to an extracellular pH lower than 7.0.…”