Cardiorespiratory stimuli: Receptor cell versus whole animal

American Zoologist, Feb 1997 by William K Milsom

SYNOPSIS. Research on the sensory inputs regulating ventilation and perfusion in vertebrates has slowly moved from studies of receptor cells to studies of the receptor proteins on receptor cells involved in signal transduction. With this new emphasis and the insights gained from this work, questions arise about the significance of specific transduction mechanisms and their link to whole animal responses to various stimuli. This is illustrated in the present chapter using two examples. The first describes pulmonary mechanoreceptors in identical locations but with different orientations. As a result of the differences in their orientation, although the receptors have identical signal transduction mechanisms and identical roles in terms of the reflex effects they elicit, they respond to different stimuli at the whole animal level. The second example suggests that different populations of 02 sensitive chemoreceptors may exist that have identical signal transduction mechanisms but, because of differences in their balance of oxygen supply to demand, may respond to different stimuli at the whole animal level. The lesson to be learned from these examples is that accompanying the growing knowledge of receptor cell function at the molecular level is a growing need to integrate this knowledge with empirical observations of whole animal responses.

Cardiorespiratory Stimuli: Receptor Cell Versus Whole Animal1

INTRODUCTION

Matching ventilation and cardiac output to the overall demands of vertebrate animals involves the central processing of a wide variety of sensory inputs from different receptor groups. An extensive literature exists on the stimulus specificities, transduction mechanisms, discharge characteristics, forms of sensory coding, locations, innervation and specific reflex effects of receptor stimulation of many of the receptors and afferent pathways involved in these processes (see Widdicombe, 1986; Coleridge and Coleridge, 1986; Milsom, 1990; Smatresk, 1990; Gonzalez et al., 1994; Sant'Ambrogio et al., 1995). While much of this work has attempted to unravel the direct mechanisms involved in the transduction of stimuli into neural discharge at the receptor level, many studies have also examined the correlation between various stimuli and the cardiorespiratory responses they elicit. Reconciling and interpreting the results of both groups of studies is not always straightforward. In this chapter I will use two examples to illustrate this point. The objective is to illustrate how differences in sensitivity of various species to different stimuli can arise from changes in the location of receptors with identical transduction mechanisms.

EXAMPLE 1: THE BEHAVIOR OF PULMONARY MECHANORECEPTORS DURING SPONTANEOUS BREATHING

Air breathing vertebrates with lungs possess receptors that convey information regarding both the rate and degree of inflation and deflation of the air breathing organ (Jones and Milsom, 1982; Coleridge and Coleridge, 1986; Milsom, 1990; Sant'Ambrogio et al., 1995). One such receptor is the slowly adapting stretch receptor (SAR). These receptors appear to be simple free nerve endings located in connective tissue within the lungs or respiratory passages (Von During et al., 1974). Their fundamental stimulus is the deformation of the nerve ending which alters membrane and channel geometry and leads to changes in ionic flux and discharge frequency. This basic signal transduction mechanism appears to be common to all proprioceptors (Schmidt, 1978). SAR in different species have discharge profiles that reflect changes in volume (Jones and Milsom, 1979), transmural pressure (Bartlett et al., 1976; Delaney et al., 1983), and wall tension (an integral of the changes in pulmonary volume and pressure) (Tagletti and Casella, 1966; McKean, 1969; Milsom and Jones, 1985). While these receptors primarily respond to the degree of change in their respective stimuli associated with each breath, they usually also are affected by the rate of change to some extent. As a consequence they exhibit a dynamic overshoot and a net increase in their discharge during inflation and a dynamic undershoot and a decrease in their discharge during deflation (Coleridge and Coleridge, 1986). Given the simple nature of these receptors, the fact that slightly different stimulus modalities cause deformation of the free nerve endings in different species is most likely a result of differences in receptor location and orientation (Coleridge and Coleridge, 1986). The possibility remains, of course, that despite their simple nature, differences in the exact stimulus modality to which different groups of receptors respond are due to structural and functional differences in the receptors themselves.

The discharge properties of these receptors have primarily been studied in artificially ventilated animals. Under these conditions (Fig. 1), lung volume, along with the pressures within the lung and trachea, as well as the pressure differences across the lung and tracheal walls (their transmural pressures), all rise and fall in concert. The increase in volume produced by the pump produces the increases in pressure. This is not the case in spontaneously breathing animals.