Four evolving concepts in molecular and clinical autonomic research

Abstract

In reflecting on decades of autonomic research, I recall the 2009 Walter B. Cannon Memorial Award Lecture, which I entitled In Search of Autonomic Balance: The Good, The Bad and The Ugly [1]. The Good was the inhibition of excessive sympathetic nerve activity by baroreceptors and by cardiac and respiratory vagal afferents. The Bad was the loss of these inhibitory signals. The Ugly was the fact that the loss of the inhibitory signals enhances the excitatory signals (e.g., from chemoreceptors and somatic afferents). The discovery of the molecular determinants of afferent mechanical and chemical signaling, their paracrine activation, and their genetic regulation have revealed new mechanisms of cardiovascular autonomic dysfunction with potential therapeutic interventions. Namely, sophisticated optogenetic techniques allow activation of specific afferent autonomic nerves [16]; and novel surgical devices and approaches are used in clinical trials involving carotid sinus, glossopharyngeal, or vagus nerve stimulation, renal denervation, carotid body resection, and cardiac neuroablation.In this invited commentary commemorating the 30th anniversary of Clinical Autonomic Research, I will highlight progress in clinical autonomic research by briefly reviewing four evolving concepts in the field. I ask for your indulgence, as I focus on experimental themes specifically pursued at the University of Iowa Cardiovascular Research Center. Consequently, other relevant autonomic concepts may not have been discussed here.

Delayed Onset Muscle Soreness and Critical Neural Microdamage-Derived Neuroinflammation

“…Correspondingly, this time overlap could have two implications. First, an intimate crosstalk between the autonomic nervous system and the Piezo2 ion channels could exist, as is insinuated by Abboud and Sonkodi et al [ 9 , 78 ], and as a result, the transient dysfunctionality of the microinjured Piezo2 could induce a transient autonomic disbalance. Even more precisely, the cardiac parasympathetic activity after an ASR, which is a full parasympathetic withdrawal [ 30 ], cannot return until the Piezo2 channelopathy is functionally regenerated or becomes unleaky in the hyperexcited states.…”

Orthostasis Is Impaired Due to Fatiguing Intensive Acute Concentric Exercise Succeeded by Isometric Weight-Loaded Wall-Sit in Delayed-Onset Muscle Soreness: A Pilot Study

“…It was noted earlier that the return of cardiac parasympathetic activity returns to pre-exercise levels only 1 to 2 days after high-intensity exercise [29], which is an overlap with the time window of the proposed transient Piezo2 channelopathy in DOMS [3]. Hence, functional crosstalk is suspected between the autonomic nervous system and the proprioceptive Piezo2 ion channels [3,35]. Correspondingly, it was put forward that Piezo2 channelopathy-derived subthreshold-imbalanced Ca 2+ currents could induce NMDA activation, and the activated NMDA receptors could have a central signaling role in this functional crosstalk during the aforementioned transient autonomic disbalance, not to mention that Piezo1-Piezo2 crosstalk might have additional importance in this process [4].…”