Asynchronous Action Potential Discharge in Human Muscle Sympathetic Nerve Activity
Authors: Klassen Stephen A. , Moir M. Erin , Shoemaker J. Kevin 
Published: June 2021

Pulse‐rhythmic bursts formed by synchronous action potential (AP) discharge characterises the firing behaviour of muscle sympathetic nerve activity (MSNA). However, complex AP discharge patterns related to multiple sites of control warrant an investigation of synchronicity in the human sympathetic system. Therefore, this study quantified the synchronicity of muscle sympathetic AP discharge in eight healthy individuals (4 females, 23 – 31 years, 170 ± 7 cm, 69 ± 13 kg, 60 ± 7 bpm, 89 ± 6 mmHg). MSNA (microneurography) was measured during baseline (BSL), −10 mmHg lower body negative pressure (LBNP), −40 mmHg LBNP, and an end‐expiratory apnea (APN; 30 ± 7 s). MSNA APs were detected from the filtered raw signal using a wavelet deconstruction approach and binned in clusters based on peak‐to‐peak amplitude (normalized within‐participant). An AP was considered to fire synchronously: 1) if its occurrence corresponded with a burst in the integrated MSNA signal (i.e., within ± 0.4 s of the burst peak), or 2) if it was one of ≥ 2 visible APs in the filtered microneurographic signal firing within ± 0.4 s of an ECG R‐wave, after adjusting for the conduction delay. All other APs were considered to fire asynchronously. At BSL, 33 ± 12 % of total AP activity was asynchronous (99 ± 48 asynchronous APs/100beats) and a pattern emerged whereby the probability of asynchronous AP firing decreased logarithmically (R2 = 0.80, P < 0.01) as AP cluster size increased. Compared to BSL (20 ± 6 bursts/min, 42 ± 7 AU), MSNA burst frequency increased on going to −10 mmHg LBNP (24 ± 6 bursts/min), −40 mmHg LBNP (35 ± 8 bursts/min), and APN (35 ± 9 bursts/min), while burst amplitude increased only with −40 mmHg LBNP (57 ± 8 AU) and APN (64 ± 14 AU) (both repeated measures analysis of variance [RM ANOVA]: P < 0.05, all Ppost‐hoc < 0.05). Compared with BSL, within‐burst AP discharge increased across all conditions (BSL: 144 ± 69 AP/min, 7 ± 2 AP/burst; −10 mmHg LBNP: 211 ± 87 AP/min, 8 ± 3 AP/burst; −40 mmHg LBNP: 410 ± 207 AP/min, 11 ± 4 AP/burst; APN: 397 ± 160 AP/min, 11 ± 3 AP/burst) (both RM ANOVA: P < 0.05, all Ppost‐hoc < 0.05). Compared to BSL, increased burst amplitude with −40 mmHg LBNP and APN was attributed to an increase in the within‐burst firing of previously active APs (BSL: 4 ± 1 clusters/burst, −40 mmHg LBNP: 5 ± 2 clusters/burst, APN: 5 ± 1 clusters/burst; RM ANOVA: P < 0.05, both Ppost‐hoc < 0.05) more so than the recruitment of new AP clusters (BSL: 14 ± 4 total clusters; −40 mmHg LBNP: 18 ± 7 total clusters; APN: 16 ± 6 total clusters; RM ANOVA: P > 0.05). However, compared to BSL (33 ± 12 %), the probability of asynchronous AP firing was reduced with −10 mmHg LBNP (26 ± 10 %), −40 mmHg LBNP (16 ± 7 %), and APN (14 ± 7 %; RM ANOVA: P < 0.05, all Ppost‐hoc < 0.05). The probability of asynchronous AP discharge was inversely and linearly related to burst frequency (β = −0.98, r2 = 0.67) and amplitude (β = −0.41, r2 = 0.20; both P < 0.01). This study suggests that: 1) integrated bursts of MSNA formed by synchronous AP firing are not separated by ‘neural silence’ but rather, by asynchronous AP discharge, and 2) smaller sympathetic APs are more likely to exhibit asynchronous discharge.Support or Funding InformationThis work was funded by a Natural Sciences and Engineering Research Council of Canada Discovery Grant.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.