Sensory Mechanisms in Mammalian Touch Receptor Cells

Abstract

The sense of touch is critical for hand dexterity that allows mammals to recognize and grasp objects. Different qualities of touch are encoded by sensory neurons with distinct properties. Shapes and curvature are encoded by Merkel cell-neurite complexes, which mediate slowly adapting type I (SAI) responses. Merkel cells, which cluster in fingertips and other highly touch-sensitive skin areas, are enigmatic epidermal cells first described in 1875. The role that these cells play in SAI responses has been debated for 40 years.Based on morphology, Merkel cells are proposed to be mechanosensory cells. If so, Merkel cells should 1) transduce force into membrane-potential changes that gate voltage-activated ion channels and 2) signal afferent neurons through synaptic transmission. Functional studies testing these predictions in intact skin have produced conflicting results. To tackle these questions, my laboratory uses a combination of mouse genetics, in vitro systems and intact electrophysiological recordings. Our in vitro studies have demonstrated that Merkel cells are intrinsically force-sensitive and that voltage-activated channels open downstream of mechanical stimuli. Moreover, Merkel cells express numerous ion channels and presynaptic proteins. Collectively, these results suggest that Merkel cells are capable of serving as touch receptor cells and pave the way to discover transduction mechanisms.To determine whether Merkel cells are necessary for touch responses, we used Cre-loxP technology to generate mice that completely lack Merkel cells in the body skin. We then used an ex vivo skin-nerve preparation to survey the classes of touch-sensitive afferents in the saphenous nerve. Although we found no significant differences in nociceptive sensory fibers, we observed a complete loss of SAI responses among light-touch receptors in mice lacking Merkel cells compared with wild-type mice. These results demonstrate that Merkel cells are required for appropriate sensory coding of light touch.