Merkel Cells in Somatosensation

Abstract

Merkel cells are rare epidermal cells whose function in the skin is still debated. These cells localize to highly touch-sensitive areas of vertebrate epithelia, including palatine ridges, touch domes and finger tips. In most cases, Merkel cells complex with somatosensory afferents to form slowly adapting touch receptors; it is unclear, however, whether mechanosensory transduction occurs in the Merkel cell, the somatosensory afferent or both. Classic anatomical results suggests that Merkel cells are sensory cells that transduce mechanical stimuli and then communicate with sensory afferents via neurotransmission. This model is supported by recent molecular, immunohistochemical and physiological studies of Merkel cells in vitro and in intact tissues. For example, Merkel cells express essential components of presynaptic machinery, including molecules required for release of the excitatory neurotransmitter glutamate. Moreover, Merkel cells in vitro and in vivo are activated by mechanical stimuli, including hypotonic-induced cell swelling. Although these findings support the hypothesis that Merkel cells are sensory receptor cells, a definitive demonstration that Merkel cells are necessary and sufficient to transduce touch awaits future studies.

Figure 1. Representative response profiles of RA, SAI and SAII afferents to touch

Extracellular recordings were made from individual somatosensory afferents using a semi-intact preparation consisting of mouse hairy skin innervated by the saphenous nerve. Plots of instantaneous firing frequency versus time are shown for an RA afferent (conduction velocity = 7 m·s^-1), SAI afferent (conduction velocity = 12 m·s^-1) and SAII afferent (conduction velocity = 11 m·s^-1). Arrows indicate the onset and offset of mechanical stimuli. The prolonged response of the RA fiber reflects vibration in the stimulus probe. Afferents were classified based on conduction velocity, adaptation properties and variance of firing frequency.

Figure 2. Structure of Merkel cell-neurite complexes

(A) A confocal micrograph shows a cluster of Merkel cell-neurite complexes in a mouse touch dome. Skin was dissected from a transgenic Math1/nGFP mouse. In these transgenic mice, Math1 enhancer sequences drive expression of nuclear-localized GFP (green) specifically in Merkel cells in the skin (Lumpkin et al., 2003). Within a touch tome, clusters of Merkel cells are innervated by branches (arrowheads) of a single SAI afferent (red), which was labeled in vivo by subcutaneous injection of the styryl dye FM5-95 (Meyers et al., 2003). (B) Schematic of a Merkel cell (green) and its somaotsensory afferent (red) in a touch dome (adapted from Iggo and Muir 1969). Merkel cells are connected to overlying keratinocytes by desmosomes and actin-filled microvilli. Large, dense core vesicles are cluster below the Merkel cell's characteristically lobulated nucleus. These vesicles are closely apposed to the afferent terminal and often cluster around synaptic densities. Merkel cells are contacted exclusively by myelinated axons.

Figure 3. Merkel cells (green) cluster in touch domes in hairy skin (A; arrowheads) and palatine ridges in oral epithelia (B; arrows)

Projections of confocal z-series show Merkel cells in intact tissue from Math1/nGFP transgenic mice.

Figure 4. Morphology of dissociated Merkel cells

Merkel cells were dissociated from the hairy skin of Math1/nGFP transgenic mice, purified by fluorescence-activated cell sorting based on GFP fluorescence (green), then cultured for two days in serum-free keratinocyte media. Actin-filled, dendritic processes were visualized by labeling Merkel cells with rhodamine-phalloidin (red). Details of the isolation and culture methods are given in Haeberle et al. (2004 and 2008).