Rebuttal from John H. Coote and Michael J. White.

Abstract

The study by D'Souza et al. (2015) provides evidence that endurance exercise training results in down-regulation of the pacemaker channel protein HCN4, with a consequent decrease in the funny current, so lengthening hyperpolarization between action potentials. We do not dispute this. However, training bradycardia does not occur without a functioning autonomic nervous system and is dependent on an increase in cardiac parasympathetic activity (Haykowsky & Tymchak, 2007; Coote & White, 2015). Part of our evidence is based on power spectral analysis of oscillations in the heart rhythm. These variations at the lower end of the frequency range (respiration, blood pressure and endocrine influenced) dominate the cardiac rhythm. Many studies have associated the degree of heart rate variability at the respiratory frequency with cardiac vagal tone. This has been criticized as having no substantial experimental basis (Stein et al. 2002; Monfredi et al. 2014; D'Souza et al. 2015). However, this is unfounded since experimental manoeuvres shown to change activity in cardiac parasympathetic nerve fibres (Davidson et al. 1976) also relate to similar changes in the respiratory-dependent peak in the power spectrum and these effects on the spectral peak are absent after cholinergic blockade (Akselrod et al. 1981; Pomeranz et al. 1985). The changes are too short term to involve down-regulation of the pacemaker channel protein HCN4. Thus an increase in the power of the respiratory peak of the spectrum of variations in heart rate following a period of endurance training would suggest an increase in cardiac parasympathetic activity. Monfredi et al. (2014), on the contrary, argue that the increase of variability is due primarily to a lower intrinsic pacemaker rate because the longer cycle lengths result in a non-linear (exponential) increase in variability of the interspike intervals. Therefore they contend that if intrinsic heart rate is lower, then a priori the heart rate variability will be greater. However, this does not accord with other evidence (Buch et al. 2002; Coote & White, 2015). In particular a comprehensive study in a group of healthy volunteers showed that inhibiting the funny current If with ivabradine did not reduce the respiratory-related peak in the spectrogram despite a significant fall in heart rate of 11 beats min–1 (Joannides et al. 2005). In conclusion, the bradycardia of endurance exercise not only depends on a decrease in intrinsic rate but also on an increase in cardiac parasympathetic activity.