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What keeps us ticking? Sinoatrial node mechano-sensitivity: the grandfather clock of cardiac rhythm

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Abstract

The rhythmic and spontaneously generated electrical excitation that triggers the heartbeat originates in the sinoatrial node (SAN). SAN automaticity has been thoroughly investigated, which has uncovered fundamental mechanisms involved in cardiac pacemaking that are generally categorised into two interacting and overlapping systems: the ‘membrane’ and ‘Ca2+ clock’. The principal focus of research has been on these two systems of oscillators, which have been studied primarily in single cells and isolated tissue, experimental preparations that do not consider mechanical factors present in the whole heart. SAN mechano-sensitivity has long been known to be a contributor to SAN pacemaking—both as a driver and regulator of automaticity—but its essential nature has been underappreciated. In this review, following a description of the traditional ‘clocks’ of SAN automaticity, we describe mechanisms of SAN mechano-sensitivity and its vital role for SAN function, making the argument that the ‘mechanics oscillator’ is, in fact, the ‘grandfather clock’ of cardiac rhythm.

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Abbreviations

AP:

Action potential

Ca2+ :

Calcium

CaMKII:

Calcium/calmodulin-dependent protein kinase II

cAMP:

Cyclic adenosine monophosphate

HCN:

Hyperpolarisation-activated cyclic nucleotide-gated channels

I f :

“Funny” current

I Kr :

Rapid delayed rectifier potassium current

I Ks :

Slow delayed rectifier potassium current

K+ :

Potassium

MDP:

Maximum diastolic potential

MSP:

Maximum systolic potential

NCX:

Sodium-calcium exchanger

LCR:

Local calcium releases

Na+ :

Sodium

RyR:

Ryanodine receptors

SACNS :

Cation non-selective stretch-activated channels

SAN:

Sinoatrial node

SDD:

Spontaneous diastolic depolarisation

SERCA:

Sarco/endoplasmic reticulum calcium-ATPase

SR:

Sarcoplasmic reticulum

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Funding

This work was supported by the Natural Sciences and Engineering Research Council of Canada (RGPIN-2016-04879 to T.A.Q.), the Heart and Stroke Foundation of Canada (G-18-0022185 to T.A.Q.), and the Canadian Institutes of Health Research (MOP 342562 to T.A.Q.). E.A.M. is supported by a British Heart Foundation Programme Grant (RG/20/6/35095).

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  1. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland

    Eilidh A MacDonald

  2. Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada

    T Alexander Quinn

  3. School of Biomedical Engineering, Dalhousie University, Halifax, Canada

    T Alexander Quinn

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MacDonald, E.A., Quinn, .A. What keeps us ticking? Sinoatrial node mechano-sensitivity: the grandfather clock of cardiac rhythm. Biophys Rev 13, 707–716 (2021). https://doi.org/10.1007/s12551-021-00831-8

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