Biology subjects

Monfredi, O.

Publications and source records attributed to Monfredi, O..

2 recordsLinked to original sources

bioRxiv2021

Universal inverse square relationship between heart rate variability and heart rate

In our previous study, we analyzed heart rate variability and heart rate from a large variety of cardiac preparations (including humans, living animals, Langendorff-perfused isolated hearts, and single sinoatrial nodal cells) in diverse species, combining our data with those of previously published articles. The analysis revealed that regardless of conditions, heart rate variability (for the purposes of the study assessed as standard deviation of beat-to-beat intervals) vs. heart rate follows a universal exponential decay-like relationship. Numerical simulations of diastolic interval variability by adding a randomly fluctuating term (Iper) to net current revealed a similar relationship. In the present study, using a Taylor series, we found that this relationship is, in fact, inverse square, and we derive an explicit formula for the standard deviation (sd) of the cycle length (CL) as a function of heart rate (HR) with biophysically meaningful parameters: sd(CL)=sd(Iper)*(60,000/mean(HR) -APD)^2/({Delta}V*C), where CL is in ms, HR in beats per minute, Iper in pA, APD in ms is an average AP duration of pacemaker cells, C in pF is cell membrane capacitance, and {Delta}V is the magnitude of diastolic depolarization in mV. This relationship gives direct insight into heart rate variability mechanisms at the basic level of individual pacemaker cells, i.e. their intrinsic CL variability linked to stochastic operation of ion channels (both Ca release and cell membrane channels) generating Iper. Our explicit formula may be also used for a more precise biomedical interpretation of heart rate variability after respective corrections for heart rate.

biophysics↗

bioRxiv2021

β-adrenergic stimulation synchronizes a broad spectrum of action potential firing rates of cardiac pacemaker cells towards a higher population average

The heartbeat is initiated by pacemaker cells residing in the sinoatrial node (SAN). SAN cells generate spontaneous action potentials (APs), i.e. normal automaticity. The sympathetic nervous system increases heart rate commensurate with cardiac output demand via stimulation of SAN {beta}-adrenergic receptors ({beta}AR). While SAN cells reportedly represent a highly heterogeneous cell population, the current dogma is that in response to {beta}AR stimulation all cells increase their spontaneous AP firing rate in a similar fashion. The aim of the present study was to investigate cell-to-cell variability in the responses of a large population of SAN cells. We measured {beta}AR responses among 166 single SAN cells isolated from 33 guinea pig hearts. In contrast to the current dogma, the SAN cell responses to {beta}AR stimulation substantially varied. In each cell, changes in AP cycle length highly correlated (R2=0.97) with the AP cycle length before {beta}AR stimulation. While, as expected, on average the cells increased their pacemaker rate, greater responses were observed in cells with slower basal rates, and vice versa, cells with higher basal rates showed smaller responses, no responses, or even decreased their rate. Thus, {beta}AR stimulation synchronizes the operation of the SAN cell population towards a higher average rate, rather than uniformly shifting the rate in each cell, creating a new paradigm of {beta}AR-driven fight-or-flight response among individual pacemaker cells.

biophysics↗