The autonomic nervous system concept at the heart of the matter

I read with great interest Drs Barboi and Macefield's article in the November 15 issue, 2025, of the Journal of Physiology entitled ‘The autonomic nervous system: time for a conceptual reframing?’ (Barboi & Macefield, 2025). They are to be commended for their scholarly and meticulous overview of the topic. According to my understanding the authors offered no definitive answer to whether this point in time has been reached, or when ‘the ANS concept’ is appropriate apart from when referring ‘to the organism as a whole’. Therefore the matter appears open for discussion, and I take the opportunity. The article is written with a neurologist's and neuroscientist's bias, and I offer another bias being a clinical cardiologist/electrophysiologist, teacher and scientist. I will here focus on the sino-atrial node (SAN) cells and their automaticity. To set the record straight the SAN cells are contractile myocardial cells with some properties like that of neurons, but they are not neurons (as stated on page 6728, left column, first paragraph). The task of the SAN cells is to initiate the beating of the electro-mechanical heart around 100,000 times per 24 h. The net result can be studied by their beating frequency (from here: heart rate (HR)) and beating interval variability (BIV). Rosenblueth and Simeone in 1934 reported their feline experiments on stimulating the vagal nerve and/or stellate ganglion and referred to them as ‘autonomic nerves’. They introduced ‘decelerator’ for the inhibitory action of stimulating the vagal nerve and ‘accelerator’ for the ‘excitatory’ action of stimulating the stellate ganglion, an accurate description to this date. At the end of the 1960s, Jose and Taylor (1969) showed that ‘blockade of cardiac autonomic nervous activity’ could be achieved pharmacologically in humans by an intravenous injection of propranolol 0.2 mg/kg body weight (b.w.) (ẞ-adrenergic antagonist) and atropine 0.04 mg/kg b.w. (muscarinic receptor antagonist). They named the result the ‘intrinsic heart rate’ (IHR), which varied interindividually within a physiological range. The same year the first cardiac transplant – now a routine surgical procedure – was performed in humans and confirmed that the donor heart had an IHR sufficient to keep the recipient alive but with impaired cardiovascular adaptability (Awad et al., 2016). Therefore the heart might work ‘autonomically’ in relation to the brain. However around the heart are several important ganglia, the exact function of which remains to be elucidated. How do the ‘autonomic’ SAN cells work? Their automaticity is primarily based on a membranous (action potential) clock coupled with an intracellular sarco-plasmatic calcium clock, with phosphorylation of the crucial proteins as a driving force and the mitochondria as the crucial fueling source of ATP. The cells with the highest automaticity/depolarization rate within the SAN entrain the adjacent cells by direct cell-to-cell coupling. Yaniv and Lakatta in one study on rabbit hearts compared the HR and BIV complexity (1) in vivo with the heart innervated, (2) in vivo with the heart denervated, (3) in isolated SAN tissue (without neural influence) and (4) in isolated single SAN cells (Yaniv et al., 2014). Isolated cells were exposed to isoproterenol (ẞ-adrenergic agonist) and carbachol (cholinergic agonist). They showed that HR and BIV complexity were the result of a combination of cellular intrinsic periodicity and neural influence (ẞ-adrenergic and cholinergic agonists). The circadian variation in the SAN cell automaticity is however modulated not only by the neural input but also by other factors, for example, atrial stretch (Yaniv & Lakatta, 2015). The BIV complexity of isolated SAN cells differed from the three other conditions by a less organized activity, in fact like what we described in patients with the sick sinus syndrome where the BIV was like white noise, that is, completely randomized (Bergfeldt & Haga, 2003). Returning now to the article by Drs Barboi and Macefield, it was obviously intended for the readership of the Journal of Physiology. I learned a lot and especially took to my heart and mind the following statement: ‘New terms used for new ideas must be increasingly accurately descriptive, and magical naming should not substitute for understanding (Blessing 1997; Popper 1979)’ (page 6726, left column, second paragraph). From the perspective of explaining how the very small SAN and its cells keep doing the job incessantly, why transplantation of a completely denervated heart is possible and the consequences for cardiovascular adaptability and why the heart usually ends up at an IHR of ∼90 beats per minute also in diseases accompanied by severe visceral neuropathies (e.g. diabetes, chronic kidney disease, amyloid neuropathy), it is definitely helpful to discuss the neural input to the SAN as consisting of two limbs of the nervous system with opposing effects. Is the autonomic nervous system (ANS) concept necessary? Or ‘autonomic’? No. Neither is ‘visceral’, which presumably is even further from an intuitively understandable description especially by also including the skin. But the ANS term might be helpful, because it has a long history and might be perceived as familiar and as something outside our control. I do not think it is controversial that we use different descriptions/language when we address patients about the /likely/ mechanism of their symptoms, the therapeutic alternatives and their mode of actions than when we address students, clinicians and scientific experts. The authors write: ‘Clinicians continue to understand visceral integration as automatic, involuntary and separate from somatic and emotional integration’ (p. 6726, right hand column, first paragraph). In my experience this is a pessimistic view underestimating the insights gained at least in cardiology; for example, depression is a risk factor for ischemic heart disease, stress-induced cardiomyopathy (also known as Takotsubo cardiomyopathy and the broken-heart syndrome) mimics myocardial infarction, alarm clocks might trigger arrhythmia in long QT syndrome type 2, and so on. Consequently such insights influence how we deal with our patients’ problems and what we teach our students and aspiring colleagues. Finally is it time to reframe the ANS concept and its opposing limbs? It is probably a matter of the context, but I am not convinced that ‘visceral processing function’ is ‘increasingly accurately descriptive’. That is for the reader to decide. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. None declared. Sole author. None.