Molecular Bases for High (Hf) and Low Frequency (Lf) Bands: A New Approach to Heart Rate Variability Analysis

Abstract

Heart Rate Variability (HRV) in Frequency‐domain estimate the distribution into low‐frequency (LF: 0.04–0.15 Hz) and high‐frequency (HF 0.15–0.4 Hz) bands. On the other hand, when analyzing norepinephrine and acetylcholine cell signalling time kinetics, the summation of such times once converted to frequencies in Hertz, match the previously mentioned LF and HF values.Materials and MethodsGoogle Scholar databases and National Library of Medicine, were searched for articles published from 2000 to 2019 related to the time kinetics involved in cell signaling, with the following combination of terms: 1) “Title (TI) = (FRET) AND TI = (BRET) OR ‘Activation time B1 adrenergic’ OR ‘Activation time M2 muscarinic’ OR ‘Gs Protein Activation’ OR ‘Gi Protein Activation’ ‘Time Kinetics’ OR ‘Adenylate Cyclase’ ‘Activation HCN4’ OR ‘Nodal Pace Marker’ OR ‘In Vitro Model Cells')]”. The inclusion criteria for each study included the ligand‐receptor interaction and time related signalling cascade involved in the depolarization or hyperpolarization of cells. Both database searches yielded 7 studies matching the inclusion criteria. Once all the times of cell signalling cascade were found or estimated for all receptors, such times were summed, they were converted to Hertz using the inverse relationship between time and frequency.RESULTSDatabase searches yielded 7 studies matching the inclusion criteria. For B1‐Adrenergic Receptor cell signalling cascade the estimated times were: Ligand‐Receptor‐Activation (0.045 s), Receptor Gs protein interaction (0.044 s), Gs protein activation (0.369 s), Adenylate Cyclase activation (28.8s), cAMP mediated activation of HCN4 (0.461 s), for a total of 29.76 seconds, yielding 0.0336 Hz.For M2‐Cholinergic Receptor the estimated times were: Ligand‐Receptor activation (0.750 s), Receptor Gi protein interaction (12 ns**), Gi protein activation (1 s), and Gi mediated Adenylate Cyclase inactivation (3 s), for a total of 4.75 seconds, yielding 0.211 Hz.DISCUSSIONB1‐Adrenergic Receptor cell signaling summed 29.76 seconds, yielding 0.0336 Hertz, a very close value to the 0.04 Hz of LF band. On the other hand, M2 Cholinergic receptor cell signalling time was 4.75 s, yielding 0.211 Hz, a value within the HF band range of 0.15 to 0.4 Hz. Such results coincide with the possibility of direct correlation of biochemical cell signalling and HF and LF bands spectrums. However due to the scarcity of biochemical studies, it is important to mention that during the estimation process there was two issues worth mentioning. First, B1 Adrenergic Receptor Gs Adenylate cyclase activation was roughly estimated. Second, for M2 Cholinergic Gi mediated AC inhibition, a A2‐Adrenergic receptor model was used. Despite the previously mentioned limitations, the current study results suggest the possibility that LF and HF band spectrum could be refined into smaller range of Hertz segments, which might correspond to the summation of time kinetics involved in cell signalling cascade related to the different adrenergic or cholinergic receptor subtypes.Support or Funding InformationPROSEIMThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.