The Effects of Hypoxia on Slowly Adapting Type I (SAI) Cutaneous Mechanoreceptors in the Cat and Rat

Abstract

In whatever mammalian receptor system Merkel cells are found, they are always associated with a characteristic slowly adapting response. The role of Merkel cells in the transduction process of slowly adapting Type I cutaneous mechanoreceptors (SAI receptors or touch domes) of rats and cats was investigated by mechanical and electrical stimulation of SAI receptors and their afferent fibers in an O₂-depleted environment. Circulatory hypoxia was produced either by ventilating animals with N₂ or by recirculating venous blood around a limb. In both these experimental preparations, the results obtained were identical. For receptor failure to occur, it was found necessary to have an O₂-depleted environment on the limb surface. This was achieved by passing N₂ into a gas-tight polythene sock placed over the limb. Replacement of N₂ within the polythene sock with O₂ was sufficient to bring about receptor recovery, irrespective of arterial blood PO₂ levels. There was an inverse linear relationship between receptor response and time when touch domes were stimulated with N₂ around the limb. In contrast, the replacement of N₂ around the limb with O₂ produced an exponential increase in the response with time. Correlated with receptor failure was a significant reduction in the number of dense-cored vesicles normally found in the Merkel cell cytoplasm adjacent to the nerve ending innervating the cell. Receptor recovery was associated with a return in the number of dense-cored vesicles back to that found in control cells. Hypoxia had no effect on the level of electrical stimulation necessary to initiate an action potential in the afferent fiber, even though the response of SAI receptors to mechanical stimulation had ceased. The results indicate that Merkel cell dense-cored vesicles are necessary for the characteristic slowly adapting response of SAI mechanoreceptors and that this may be due to the secretion of a transmitter substance stored within the vesicles.

Merkel cells and their associated nerve terminals are found in slowly adapting Type I (SAI) cutaneous mechanoreceptors and in other slowly adapting receptors of hairy and glabrous skin (Cauna, 1962; Iggo and Muir, 1963; Munger, 1965; Andres, 1966). Ever since Merkel (1875) first described them in the hairy skin of several animal species, they have been the subject of much debate. Merkel believed that these cells and their accompanying nerve endings were responsible for converting physical stimuli applied to the skin into neural activity in the nerve ending. This hypothesis received support almost 100 years later when Iggo and Muir (1969) described in detail the structure of the Merkel cell and its adjacent nerve terminal in SAI receptors and the distinctive physiological response of the latter to mechanical stimulation. Later Horch et al. (1974) analyzed the discharge pattern produced by the SAI mechanoreceptor and concluded that the most likely cause of the characteristic response to mechanical stimulation was transmitter release by the Merkel cells.

However, this hypothesis has not received universal support. Kasprzak et al. (1970) found that in newborn kittens the receptor system was functional even when the number of Merkel cells present was low. This, they suggested, was evidence that it was the neuron terminal that was the mechaiiotransducer and not the Merkel cell. Gottschaldt and Vahle-Hinz (1981,1982) agreed with this view and further proposed that either the Merkel cells were target cells for the postnatal arborization of the Type I nerve fiber, or they were merely the passive abutments for the mechanosensitive ending.

A characteristic feature of the Merkel cells is the presence of numerous membrane bound dense-cored vesicles, which are in greatest concentration in the cytoplasm between the nucleus and the plasma membrane adjacent to the nerve ending. In an investigation of the role of the Merkel cell in the transduction process, Anand et al. (1979) tested the effects of extreme hypoxia on the response of the receptor to mechanical stimulation and on the number and distribution of the vesicles. Histological examination of the Merkel cells in hypoxic receptors fixed at the time they had ceased to respond to mechanical stimulation revealed an almost total loss of vesicles. This present work confirms and extends these results and examines quantitatively the correlation between receptor failure and the loss of Merkel cell vesicles. Preliminary reports have been published (Cooksey et al., 1983; Iggo and Findlater, 1984).