Asynchronous action potential discharge in human muscle sympathetic nerve activity

Abstract

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 n...

Heterogeneous baroreflex control of sympathetic action potential subpopulations in humans

“…During orthostatic stress, enhanced baroreflex gain results in greater sympathetic AP firing for a given reduction in DBP but also prevents exaggerated sympathetic responses, as the arterial baroreflex fundamentally represents an inhibitory process (Wallin & Eckberg, 1982;Dampney, 1994). To our knowledge this study was the first to examine baroreflex control of AP discharge during physiological stress and illustrates that the arterial baroreflex strongly controls the behaviour of medium APs which are synchronized to fire in most bursts of MSNA (Macefield et al 1994;Klassen et al 2019).…”

“…This pattern was likely exposed more clearly in the present study due to the emphasis on cluster normalization and because we extracted all detected APs regardless of whether they fired within or between bursts, whereas our previous study focused solely on the synchronized APs forming integrated bursts (Salmanpour & Shoemaker, 2012). This analysis strategy was based on a recent observation that about 30% of sympathetic APs at BSL fire asynchronously between MSNA bursts in healthy young individuals, with the smallest APs expressing the greatest proportion of asynchronous activity (Klassen et al 2019). While we did not examine the baroreflex gain 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Fig.…”

“…This study evaluated data from 12 healthy young individuals (6 females, 26 ± 3 years, 171 ± 8 cm, 70 ± 12 kg) that arose from two groups (each n = 6, 3 females): a prospective analysis (some participants provided baseline data for a separate study (Klassen et al 2019)), and a retrospective analysis of a subset of a larger study that has been published elsewhere to address unrelated hypotheses (Usselman et al 2013(Usselman et al , 2015Badrov et al 2015). All participants were normotensive and free of cardiovascular or neurological diseases.…”

“…Also, small APs may not be governed strongly by the arterial baroreflex. In fact, we reported that 30% of total APs fired asynchronously outside baroreflex-gated bursts at baseline, with smaller APs expressing the greatest proportion of asynchronous discharge (Klassen et al 2019). However, baroreflex regulation of the differently sized sympathetic AP subpopulations has only been studied under baseline conditions (Salmanpour & Shoemaker, 2012); the impact of physiological stress on baroreflex control of AP discharge remains unclear.…”

“…To do so, we measured the baroreflex gain for each AP cluster during a range of baroreceptor unloading using LBNP. Based on preliminary observations (Salmanpour & Shoemaker, 2012;Klassen et al 2019), the hypothesis predicts that on going from BSL to LBNP, baroreflex functions for medium APs will express the greatest increase in slope and upward resetting. Also, preliminary data (Limberg et al 2018) point towards reductions in baroreflex control over the smallest APs with orthostatic stress.…”