Asynchronous action potential discharge in human muscle sympathetic nerve activity

Abstract

What strategies are employed by the sympathetic system to communicate with the circulation? Muscle sympathetic nerve activity (MSNA) occurs in bursts of synchronous action potential (AP) discharge, yet whether between-burst asynchronous AP firing exists remains unknown. Using multiunit microneurography and a continuous wavelet transform to isolate APs, we studied AP synchronicity within human MSNA. Asynchronous APs were defined as those which occurred between bursts. Experiment 1 quantified AP synchronicity in eight individuals at baseline (BSL), -10 mmHg lower body negative pressure (LBNP), -40 mmHg LBNP, and end-expiratory apnea (APN). At BSL, 33 ± 12% of total AP activity was asynchronous. Asynchronous discharge was unchanged from BSL (67 ± 37 AP/min) to -10 mmHg LBNP (69 ± 33 AP/min), -40 mmHg LBNP (83 ± 68 AP/min), or APN (62 ± 39 AP/min). Across all conditions, asynchronous AP probability and frequency decreased with increasing AP size. Experiment 2 examined the impact of the ganglia on AP synchronicity by using nicotinic blockade (trimethaphan). The largest asynchronous APs were derecruited from BSL (11 ± 4 asynchronous AP clusters) to the last minute of the trimethaphan infusion with visible bursts (7 ± 2 asynchronous AP clusters). However, the 6 ± 2 smallest asynchronous AP clusters could not be blocked by trimethaphan and persisted to fire 100 ± 0% asynchronously without forming bursts. Nonnicotinic ganglionic mechanisms affect some, but not all, asynchronous activity. The fundamental behavior of human MSNA contains between-burst asynchronous AP discharge, which accounts for a considerable amount of BSL activity.NEW & NOTEWORTHY Historically, sympathetic nerve activity destined for the blood vessels supplying skeletal muscle (MSNA) has been characterized by spontaneous bursts formed by synchronous action potential (AP) discharge. However, this study found a considerable amount (~30% during baseline) of sympathetic AP discharge to fire asynchronously between bursts of human MSNA. Trimethaphan infusion revealed that nonnicotinic ganglionic mechanisms contribute to some, but not all, asynchronous discharge. Asynchronous sympathetic AP discharge represents a fundamental behavior of MSNA.

Keywords: action potential; asynchronous discharge; microneurography; muscle sympathetic nerve activity; paravertebral ganglia; sympathetic nervous system; sympathetic neural recruitment.

Fig. 1.

Criteria employed to discriminate between synchronous and asynchronous action potentials (AP) during analysis. Electrocardiogram (ECG), integrated muscle sympathetic nerve activity (MSNA), filtered MSNA, and detected APs from 1 individual. Synchronous AP criterion A: APs were considered to fire synchronously if their occurrence corresponded with ± 0.4 s from the peak of an integrated MSNA burst. Synchronous AP criterion B: when no integrated burst was apparent, APs were considered to fire synchronously if at least 2 APs were visible in the filtered neurogram and occurred within ± 0.4 s of an ECG R-wave. For heart rates (HRs) ≥75 beats/min the window for synchronous APs was reduced to one-half of the R-R interval for that beat. The neurogram was corrected for the conduction delay. Arrows indicate 3 APs visible within the filtered neurogram. APs that did not satisfy these 2 criteria were deemed asynchronous. *1 asynchronous AP detected in this section of data.

Fig. 2.

Representative data from 1 participant depicting the electrocardiogram (ECG), blood pressure (BP), integrated muscle sympathetic nerve activity (MSNA), filtered MSNA, and detected action potentials (AP) at baseline (BSL; A), −10 mmHg lower body negative pressure (LBNP; B), −40 mmHg LBNP (C), and onset of end-expiratory apnea (APN; D). Data selections illustrate synchronous AP discharge (indicated by *), often forming bursts and asynchronous APs firing between bursts for each study condition. Notice in the APN data selection, as indicated by arrow and dashed line, that some asynchronous APs fired without cardiac rhythmicity between two adjacent bursts of synchronous APs. All neurograms were corrected for the conduction delay.

Fig. 3.

Probability (A) and frequency (B) of asynchronous action potential (AP) discharge at baseline (BSL), −10 mmHg lower body negative pressure (LBNP), −40 mmHg LBNP, and end-expiratory apnea (APN). Means ± SD for each condition are represented by filled circles and error bars. Individual data are represented by thin gray lines. P values for main effect of condition obtained with repeated-measures ANOVA are reported. *P_{post hoc} < 0.05 vs. BSL.

Fig. 4.

Representative morphologies of synchronously (left black tracing within each panel) and asynchronously (right gray tracing within each panel) discharging action potential (AP) clusters, detected in 1 participant during baseline (BSL), −10 mmHg lower body negative pressure (LBNP), −40 mmHg LBNP, and end-expiratory apnea (APN). AP clusters were binned based on peak-to-peak amplitude; n = 1,986 synchronous and n = 454 asynchronous APs fired across all conditions. Thick and thin lines represent means and SDs of cluster amplitude, respectively. Clusters without a mean AP tracing indicate no AP activity across all study conditions.

Fig. 5.

Asynchronous action potential (AP) probability (A) and asynchronous AP frequency (B) vs. normalized AP cluster (normalized to 10 clusters; e.g., cluster 1 represents 0–10% of largest cluster detected across all conditions) at baseline (BSL), −10 mmHg lower body negative pressure (LBNP), −40 mmHg LBNP, and end-expiratory apnea (APN). A and B: means ± SE for each cluster are represented by filled circles and error bars. A: data from each condition were fitted with a logarithmic function.

Fig. 6.

Representative data from 1 participant depicting electrocardiogram (ECG), blood pressure (BP), integrated muscle sympathetic nerve activity (MSNA), filtered MSNA, and detected action potentials (AP) at baseline (BSL; A), the last minute of the trimethaphan infusion with visible bursts (TM Last Min; B), and the period of the trimethaphan infusion with no visible bursts (TM No Burst; C). Data selections illustrate synchronous AP discharge (indicated by *), often forming bursts and asynchronous APs firing between bursts for BSL and TM Last Min and without bursts in the TM No Burst condition. All neurograms were corrected for the conduction delay.

Fig. 7.

Asynchronous action potentials (AP) probability (A) and asynchronous AP frequency (B) vs. normalized AP cluster (normalized to 10 clusters; e.g., cluster 1 represents 0–10% of largest cluster detected across all conditions) at baseline (BSL), the last minute of trimethaphan with visible bursts (TM Last Min), and the period of the trimethaphan infusion with no visible bursts (TM No Burst). A and B: means ± SE for each cluster are represented by filled circles and error bars. A: data from BSL and TM Last Min were fitted with logarithmic functions. No error bars are visible for TM No Burst, as all clusters expressed 100% asynchronous probability (n = 7). B: no error bars are visible for BSL firing frequency of larger clusters due to small variability (n = 7). Notice that at BSL all sized APs fired asynchronously but smaller APs expressed the greatest probability of asynchronous activity. Trimethaphan derecruited larger asynchronous APs but had no impact on the overall firing frequency of asynchronous APs.