Pulmonary stretch receptor spike time precision increases with lung inflation amplitude and airway smooth muscle tension

Abstract

Slowly adapting pulmonary stretch receptors (SARs) respond to different lung inflation volumes with distinct spike counts and patterns, conveying information regarding the rate and depth of breathing to the cardiovascular and respiratory control systems. Previous studies demonstrated that SARs respond to repetitions of the same lung inflation faithfully, suggesting the possibility of modeling an SAR's discrete response pattern to a stimulus using a statistically based method. Urethane-anesthetized rabbit SAR spike trains were recorded in response to repeated 9-, 12-, and 15-ml lung inflations, and used to construct model spike trains using K-means clustering. Analysis of the statistics of the responses to different lung inflation volumes revealed that SARs fire with more temporal precision in response to larger lung inflations, because the standard deviations of real spikes clustered around the modeled spike times of responses to 15-ml stimuli were smaller than those produced by 12 or 9 ml, even at the same absolute firing frequencies. This implied that the mechanical coupling of SAR endings with pulmonary tissue is critical in determining spike time reliability. To test this, we collected SAR responses during bronchial constriction, compared them with those produced by the same SARs under normal airway resistance, and found that their firing reliability improved during bronchial constriction. These results suggest that airway distension and mechanical coupling of the receptor endings with the airway wall (partially determined by smooth muscle tone) are important determinants of SAR spike time reliability.

Fig. 1.

Response spike count histogram for a low-threshold slowly adapting pulmonary stretch receptor (SAR) in response to a repeated lung inflation stimulus. This was the largest variability in spike count for any neuron in this study.

Fig. 2.

Raster plots of SAR responses to repeated lung inflations. For clarity, only 100 randomly selected responses are shown in response to inflations of 9 (top), 12 (middle), and 15 ml (bottom). Spike times appear more consistent in response to higher (15 ml) than lower (9 ml) inflation volumes. TP, tracheal pressure.

Fig. 3.

K-means clustering of responses to 3 lung inflation volumes by the same SAR as in Fig. 2. Spike probability (shaded histograms, 0.1-ms bins) and model spike times (black data points) are shown for 9 (top), 12 (middle), and 15 ml (bottom).

Fig. 4.

Standard deviation (SD) of spike responses during lung inflation stimuli. SDs (data points, left y-axes) for the spike times associated with each model spike are shown in response to 9 (top), 12 (middle), and 15 ml (bottom). The TP waveforms (solid line, right y-axes) are shown for reference. Note that left y-axis scales differ in each plot. Time axis label (bottom) applies to all plots.

Fig. 5.

SD vs. the rate of change in TP (dTP/dt) during lung inflation stimuli. SDs (points, right y-axes) for spike times associated with each cluster are shown in response to 9 (top), 12 (middle), and 15 ml (bottom). The concomitant dTP/dt waveforms (solid line, left y-axes) are shown for each lung inflation stimulus. Note that the y-axis scales are different for each plot. Time axis label (bottom) applies to all plots.

Fig. 6.

Comparison of SDs at similar firing frequencies suggests a strong effect of inflation volume. Aa: SDs of spike clusters are given for spikes produced in response to 9-ml (asterisks), 12-ml (circles), and 15-ml lung inflations (triangles). A rectangle outlines 3 data points within 5 Hz of each other used to populate a 3-way comparison histogram describing rank orders of near-identical firing rates, shown in Ab. Ab: rank order of 3-way (top) and 2-way (bottom) comparisons of SDs in Aa. Horizontal shaded lines indicate levels expected for a uniform distribution, if lung inflation volume had no effect on SD. For this neuron, 2-way comparisons were too rare to generate a distribution that varied significantly from the uniform distribution. B: global average percentages (ave.%) for each rank order are shown after conversion of counts to percentages for each SAR and indicate the strong preference for the 9 > 12 > 15-ml rank order. C: distribution of the most frequently occurring rank order for 3-way comparisons over all 19 SARs once again demonstrates the dominance of the 9 > 12 > 15-ml observation. Shaded lines are as defined in Ab.

Fig. 7.

SDs as a function of 2 stimulus variables. A and B: SDs of spikes produced in response to 9-ml (blue), 12-ml (red), and 15-ml stimuli (green) for 2 typical high-threshold SARs. C and D: SD vs. TP and dTP/dt for 2 low-threshold SARs. E: SD vs. TP and dTP/dt for an atypical low-threshold SAR. Note the different z-axis (SD) scales for different plots. F: normalized, averaged SDs (+SDs) over all, only high threshold (high thresh), or only low threshold SARs (low thresh). Bar colors designate the same stimuli as in scatter plots. P values for pairwise comparisons: 1, 9.99 × 10⁻⁷; 2, 0.0971; 3, 8.00 × 10⁻⁵; 4, 0.00255; 5, 0.4013; 6, 0.0191; 7, 5.41 × 10⁻⁵; 8, 0.0758; 9, 2.82 × 10⁻⁴.

Fig. 8.

Effects of bronchial constriction on TP waveform and spike response. A: typical response (spike times, vertical lines) of a high-threshold SAR to a 9-ml lung inflation and its associated TP waveform (solid line) during normal airway smooth muscle tone. B: same data as in A, for the same SAR, during bronchial constriction. C: superimposed TP traces for both conditions. Dashed and solid TP traces are bronchial constriction and normal conditions, respectively. Dashed (bronchial constriction) and solid (control) horizontal bars above TP traces show the periods of action potential discharge for the respective traces.

Fig. 9.

Effects of bronchial constriction on SD. Top: SD vs. TP and dTP/dt for a typical high-threshold SAR in response to 9-ml lung inflation in conditions of normal airway resistance (control; red) or bronchial constriction (blue). Middle: SD vs. TP and dTP/dt for the same SAR as at top, under the same conditions, but in response to 12-ml lung inflation. Bottom: summary data, normalized and averaged over all nine SARs. Bar colors designate the same conditions as in scatter plots.