Spectrum of myelinated pulmonary afferents (III) cracking intermediate adapting receptors

Abstract

Conventional one-sensor theory (one afferent fiber connects to a single sensor) categorizes the bronchopulmonary mechanosensors into the rapidly adapting receptors (RARs), slowly adapting receptors (SARs), or intermediate adapting receptors (IARs). RARs and SARs are known to sense the rate and magnitude of mechanical change, respectively; however, there is no agreement on what IARs sense. Some investigators believe that the three types of sensors are actually one group with similar but different properties and IARs operate within that group. Other investigators (majority) believe IARs overlap with the RARs and SARs and can be classified within them according to their characteristics. Clearly, there is no consensus on IARs function. Recently, a multiple-sensor theory has been advanced in which a sensory unit may contain many heterogeneous sensors, such as both RARs and SARs. There are no IARs. Intermediate adapting unit behavior results from coexistence of RARs and SARs. Therefore, the unit can sense both rate and magnitude of changes. The purpose of this review is to provide evidence that the multiple-sensor theory better explains sensory unit behavior.

Keywords: afferent; lung; receptor; sensory unit; vagus nerve.

Fig. 1.

This rabbit mechanosensory unit demonstrates the adaptation rate is inflation pressure dependent. AIs for 20 (30%, 270/190, peak/2nd sec mean), 30 (45.2%, 310/170), 40 (56.3%, 320/140) cmH₂O are different. The unit activity has two components when the lung inflated to 20, 30, and 40 cmH₂O. At 20 cmH₂O, the rapidly adapting component is small with a significant slowly adapting component. As the inflation pressure increases, the rapidly adapting component increased, whereas the slowly adapting component decreased. That is, the sustained activity of slowly adapting receptor (SAR) is highest at 20 cmH₂O and lowest at 40 cmH₂O, indicating a deactivation of SAR.

Fig. 2.

A sensory unit showing changes in discharge pattern during different lung inflation pressure. Note that higher inflation pressure produces a faster adaptation rate (AI). The lungs were sequentially inflated to 15 cmH₂O (A, 75%), 12 cmH₂O (B, 65%), and 7 cmH₂O (C, 28%). Unit activity ceases after adaptation at 15 cmH₂O. The activity after adaptation reached a plateau at 12 and 7 cmH₂O. Clearly, this unit has an initial rapidly adapting receptor (RAR) component and a delayed slowly adapting receptor (SAR) component. Adapted from Fig. 5 in Ref. .

Fig. 3.

A double staining approach to illustrate slowly adapting receptor (SAR) sensory structures identified in rabbit airways. Na⁺-K⁺-ATPase stains all structures in the sensory unit (red), whereas myelin basic protein (MBP) stains the myelin sheath (green) and shows yellow (costaining) in the composite figure (top-right and bottom parts). Clearly, the axon is demyelinated before it reaches the end formation. Thus, the receptor can be identified (pure red portions without costain with MBP). Top (small airway, 300 µm in diameter): the parent axon of the sensory structure is running from the bottom up. It gives off three branches, indicated by white arrows 1, 2, and 3 in the top left. Its first branch is at the bottom of the figure, the second one in the middle part, and the third one at the upper part. Six receptors can be identified in this microscopic view (1 in the first branch, 3 in the second, and 2 in the third). They are showing red on double stain. Bottom (trachea): two parent axons (one starts at top-right and one at low left, indicated by white arrows 1 and 2) can be identified. The top-right sensory structure (1) has 9 receptors and the bottom-left one (2) has 13 receptors. Insets are enlarged to illustrate the sensory receptors. Adapted from Fig. 1 in Ref. with permission.

Fig. 4.

Recording of a single slowly adapting receptor (SAR) unit in a single ventilator cycle. This unit has two receptive fields identified. A: control, the unit activity represents a low-threshold pattern; and (B) after blocking one field with lidocaine. The unit represents a high-threshold pattern. The bar in (A) indicates where unit activity switches between encoders. The arrow in (B) indicates where discharge of a high-threshold encoder is about to exceed the low-threshold encoder. Drawing two vertical lines at the arrow in (B) and at the beginning of the bar in (A) divides figure (A) into three sections. The activity during deflation (first and third sections) is determined by the low threshold encoder (with a low peak discharge frequency), whereas the activity during inflation (second section) is determined by the high-threshold encoder. Thus, the pacemaker switches back and forth between the two encoders within a ventilator cycle. Adapted from Fig. 3 in Ref. with permission.

Fig. 5.

A rabbit mechanosensory unit responded to both lung inflation and deflation with an intermediate adaptation rate, i.e., both had an initial rapidly adapting component and a delayed slowly adapting component. A, C, E: lung inflation (30 cmH₂O) and B, D, F: lung deflation (−4 cmH₂O). A and B: the precontrols. C and D: after one receptive field was blocked by injection of 2% lidocaine (10 µL). Please note that the inflation response is unaffected, the slowly adapting component to lung deflation is completely blocked, and the rapidly adapting component is greatly attenuated, suggesting that inflation and deflation activities come from different encoders. E and F: postcontrols, i.e., after recovery from the anesthetics.