Cardiac Pacemaker Activity and Aging

Peters, Colin H.; Sharpe, Emily J.; Proenza, Catherine

doi:10.1146/annurev-physiol-021119-034453

Cited by 67 publications

(53 citation statements)

References 146 publications

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“…6A and 6B), we expect that it contributes to a relatively depolarized V1/2 of If in sinoatrial myocytes, consistent with studies in an IRAG knockdown mouse that show a decrease in resting heart rate (41). Since If is an important determinant of the diastolic depolarization rate and heart rate (48), these data predict that IRAG plays a physiologically relevant role in defining the magnitude of If and, consequently, heart rate.…”

Section: Irag Expression Is Predicted To Increase If In Sinoatrial Mysupporting

confidence: 80%

Isoform-specific regulation of HCN4 channels by a family of endoplasmic reticulum proteins

Peters

Myers

Juchno

et al. 2020

Preprint

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The pore-forming subunits of ion channels are regulated by auxiliary interacting proteins.Hyperpolarization-activated cyclic nucleotide-sensitive isoform 4 (HCN4) channels are critical determinants of electrical excitability in many types of cells including neurons and cardiac pacemaker cells. Here we report the discovery of two novel HCN4 regulatory proteins. Despite their homology, the two proteinslymphoid-restricted membrane protein (LRMP) and inositol trisphosphate receptor-associated guanylate kinase substrate (IRAG)have opposing effects on HCN4, causing loss-and gain-of-function, respectively. LRMP and IRAG are expected to play critical roles in regulation of physiological processes ranging from wakefulness to heart rate through their modulation of HCN4 channel function.

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Section: Irag Expression Is Predicted To Increase If In Sinoatrial Mysupporting

confidence: 80%

Isoform-specific regulation of HCN4 channels by a family of endoplasmic reticulum proteins

Peters

Myers

Juchno

et al. 2020

Preprint

Self Cite

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“…In addition to the remodeling leading to delayed and impaired cardiac impulse conduction due to a decrease in Connexin 43 (Cx43) expression with aging [ 5 , 61 , 62 ], there are also electrophysiological alterations in the sinoatrial node involving depression of its activity, which could enhance initiation of the electrical impulse in other cells of the heart [ 63 ]. Animal studies suggest that decreased expression of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2, ICa-L current, T-type calcium current, and voltage-gated potassium (Kv) channels (Kv1.5 channels) can also play a role [ 64 – 66 ].…”

Section: Aging: Body and Heart Rhythmsmentioning

confidence: 99%

Melatonin to Rescue the Aged Heart: Antiarrhythmic and Antioxidant Benefits

Segovia-Roldán

Diez

Pueyo

2021

Oxidative Medicine and Cellular Longevity

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Aging comes with gradual loss of functions that increase the vulnerability to disease, senescence, and death. The mechanisms underlying these processes are linked to a prolonged imbalance between damage and repair. Damaging mechanisms include oxidative stress, mitochondrial dysfunction, chronodisruption, inflammation, and telomere attrition, as well as genetic and epigenetic alterations. Several endogenous tissue repairing mechanisms also decrease. These alterations associated with aging affect the entire organism. The most devastating manifestations involve the cardiovascular system and may lead to lethal cardiac arrhythmias. Together with structural remodeling, electrophysiological and intercellular communication alterations during aging predispose to arrhythmic events. Despite the knowledge on repairing mechanisms in the cardiovascular system, effective antiaging strategies able to reduce the risk of arrhythmias are still missing. Melatonin is a promising therapeutic candidate due to its pleiotropic actions. This indoleamine regulates chronobiology and endocrine physiology. Of relevance, melatonin is an antiaging, antioxidant, antiapoptotic, antiarrhythmic, immunomodulatory, and antiproliferative molecule. This review focuses on the protective effects of melatonin on age-induced cardiac functional and structural alterations, potentially becoming a new fountain of youth for the heart.

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“…To date, several mechanisms have been proposed to account for age-related SND. The reader can find a detailed discussion about age related SND in a recent review by Peters et al (132). Interestingly, similar to other secondary forms of SND, decline of pacemaker activity with ageing is attributed to intrinsic remodeling of the SAN structure and expression of ion channels involved in automaticity.…”

Section: Secondary Forms Of Snd In Humans and Animal Modelsmentioning

confidence: 96%

Pharmacologic Approach to Sinoatrial Node Dysfunction

Mesirca

Fedorov

Hund

et al. 2021

Annu. Rev. Pharmacol. Toxicol.

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The spontaneous activity of the sinoatrial node initiates the heartbeat. Sinoatrial node dysfunction (SND) and sick sinoatrial syndrome are caused by the heart's inability to generate a normal sinoatrial node action potential. In clinical practice, SND is generally considered an age-related pathology, secondary to degenerative fibrosis of the heart pacemaker tissue. However, other forms of SND exist, including idiopathic primary SND, which is genetic, and forms that are secondary to cardiovascular or systemic disease. The incidence of SND in the general population is expected to increase over the next half century, boosting the need to implant electronic pacemakers. During the last two decades, our knowledge of sinoatrial node physiology and of the pathophysiological mechanisms underlying SND has advanced considerably. This review summarizes the current knowledge about SND mechanisms and discusses the possibility of introducing new pharmacologic therapies for treating SND. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 7, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Cardiac Pacemaker Activity and Aging

Cited by 67 publications

References 146 publications

Isoform-specific regulation of HCN4 channels by a family of endoplasmic reticulum proteins

Isoform-specific regulation of HCN4 channels by a family of endoplasmic reticulum proteins

Melatonin to Rescue the Aged Heart: Antiarrhythmic and Antioxidant Benefits

Pharmacologic Approach to Sinoatrial Node Dysfunction

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