Age-related differences in isolated rat sinus node function

Gennaro, Marco Di; Bernabei, Roberto; Sgadari, Antonio; Carosella, Luciana; Carbonin, P. U.

doi:10.1007/bf01907222

Cited by 22 publications

(13 citation statements)

References 17 publications

(13 reference statements)

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“…These changes are thought to contribute to the age-dependent declines in iHR and mHR by limiting the ability of the relatively small sinoatrial node to overcome the hyperpolarizing load of the much larger surrounding atrial tissue (41,42). In addition to these mechanisms, a decrease in excitability of individual SAMs has been proposed as a potential factor that could contribute to age-dependent reductions in iHR and mHR (14,15,43). Our present data establish that aging does indeed depress the spontaneous activity of SAMs as a result of altered membrane properties.…”

Section: Discussionmentioning

confidence: 99%

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Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

Larson

Clair

Sumner

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

118

163

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An inexorable decline in maximum heart rate (mHR) progressively limits human aerobic capacity with advancing age. This decrease in mHR results from an age-dependent reduction in "intrinsic heart rate" (iHR), which is measured during autonomic blockade. The reduced iHR indicates, by definition, that pacemaker function of the sinoatrial node is compromised during aging. However, little is known about the properties of pacemaker myocytes in the aged sinoatrial node. Here, we show that depressed excitability of individual sinoatrial node myocytes (SAMs) contributes to reductions in heart rate with advancing age. We found that agedependent declines in mHR and iHR in ECG recordings from mice were paralleled by declines in spontaneous action potential (AP) firing rates (FRs) in patch-clamp recordings from acutely isolated SAMs. The slower FR of aged SAMs resulted from changes in the AP waveform that were limited to hyperpolarization of the maximum diastolic potential and slowing of the early part of the diastolic depolarization. These AP waveform changes were associated with cellular hypertrophy, reduced current densities for L-and T-type Ca 2+ currents and the "funny current" (I f ), and a hyperpolarizing shift in the voltage dependence of I f . The agedependent reduction in sinoatrial node function was not associated with changes in β-adrenergic responsiveness, which was preserved during aging for heart rate, SAM FR, L-and T-type Ca 2+ currents, and I f . Our results indicate that depressed excitability of individual SAMs due to altered ion channel activity contributes to the decline in mHR, and thus aerobic capacity, during normal aging. O ne of the most insidious aspects of growing older is an inevitable decline in maximum heart rate (mHR), which limits maximum aerobic capacity with advancing age (1-3). The decline in mHR proceeds at approximately the same rate for all individuals, without regard for lifestyle or physical fitness (4-8). For many otherwise healthy elderly people, it is the factor that ultimately restricts the ability to live independently (9, 10).The decrease in mHR with age results primarily from a parallel age-dependent decline in "intrinsic heart rate" (iHR) (11-13), which is measured during autonomic blockade, and thus reflects the spontaneous pacemaker activity of the sinoatrial node of the heart. Although it is known that the intact sinoatrial node from aged animals contracts more slowly (14, 15) and contains fewer pacemaker myocytes (16), little is known about the functional properties of individual myocytes from the sinoatrial node of the aged heart.Sinoatrial myocytes (SAMs) are highly specialized cells that serve a primarily electrical function as cardiac pacemakers via their production of spontaneous action potentials (APs). Sinoatrial APs are characterized by a spontaneous depolarization during diastole that drives the membrane potential to threshold, thereby triggering the subsequent AP. This "diastolic depolarization" (DD) phase of the sinoatrial AP results from the coordinated activit...

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Section: Discussionmentioning

confidence: 99%

“…Although it is known that the intact sinoatrial node from aged animals contracts more slowly (14,15) and contains fewer pacemaker myocytes (16), little is known about the functional properties of individual myocytes from the sinoatrial node of the aged heart.…”

mentioning

confidence: 99%

Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

Larson

Clair

Sumner

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

118

163

View full text Add to dashboard Cite

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“…31 Previously, we reported that the intrinsic heart rate in our guinea pig model drops from 249Ϯ13 bpm at 1 day to 152Ϯ5 bpm in the 38-month-old animal. 24 In the present study, however, we tested the sensitivity of the intrinsic heart rate to the commonly deployed calcium antagonist nifedipine.…”

Section: Discussionmentioning

confidence: 99%

Declining Into Failure

2007

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Background-The spontaneous activity of pacemaker cells in the sinoatrial (SA) node controls heart rate under normal physiological conditions. Clinical studies have shown the incidence of SA node dysfunction increases with age and occurs with peak prevalence in the elderly population. The present study investigated whether aging affected the expression of Ca v 1.2 channels and whether these changes could affect pacemaker activity, in turn leading to age-related SA node degeneration. Methods and Results-The SA node region was isolated from the right atrium of guinea pigs between birth and 38 months of age. Immunofluorescence studies showed Ca v 1.2 protein was present as punctate labeling around the outer membrane of atrial cells but was absent from the center of the SA node. The area lacking Ca v 1.2-labeled protein progressively increased from 2.06Ϯ0.1 (meanϮSEM) mm 2 at 1 month to 18.72Ϯ2.2 mm 2 at 38 months (PϽ0.001). Western blot provided verification that Ca v 1.2 protein expression within the SA node declined during aging. Functional measurements showed an increased sensitivity to the L-type calcium blocker nifedipine; SA node preparations stopped beating in 100 mol/L nifedipine at 1 day old, compared with 30 mol/L at 1 month and 10 mol/L at 38 months of age. Furthermore, the amplitude of extracellular potentials declined within the center and periphery of the SA node during aging. Conclusions-The present data show Ca v 1.2 channel protein decreases concurrently with reduced spontaneous activity of the SA node with increased age, which provides further evidence of mechanisms underlying the age-related deterioration of the cardiac pacemaker.

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“…Ageing increases vagal predominance, and suppresses cardiac functions, i.e., a prolongation of R-R interval [35][36][37]. The SA node also decreases the functions with ageing, and simultaneously might compensate for the age-related deterioration [38].…”

Section: Discussionmentioning

confidence: 99%

Gender-Related Differences in a Process of the Age-Dependent Alterations of the Elements in Monkey Sino-Atrial Node

Satoh

Tohno

Minami

et al. 2010

Korean J Physiol Pharmacol

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Gender differences in the trace elements of monkey sino-atrial (SA) node were investigated in a process of age-dependent alterations. Sixty hearts from Japanese and rhesus monkeys (30 male and 30 female) used were aged ranging from 1-day-to 30-year-old. The elements were analyzed using an inductively coupled plasma-atomic emission spectrometer (ICP-AES). Advancing age decreased all the trace elements. Ca, P, S and Mg significantly decreased. The correlation coefficients of Ca and P were − 0.178±0.081 (p＜ 0.05) and − 0.088±0.022 (p＜ 0.05) in male (n=30), and − 0.095±0.026 (p＜ 0.05) and − 0.069±0.017 (p＜ 0.05) in female (n=30), respectively. The age-dependent coefficients for Fe/Ca, Zn/Ca, Fe/P, Fe/S, Zn/S, Fe/Mg and Zn/Mg were exhibited markedly in male, but all was less in female. In gender-related differences, only a ratio of P/Ca (p＜ 0.05) was significantly observed with ageing. The trace elements such as Cu, Se and Sn were less detected in the SA nodes. These results indicate that the age-dependent changes in the ratios of elements are appeared more rapidly in male monkey SA node, and the gender difference is observed in ratio of P/Ca. The different attenuations may be involved with the age-and gender-related SA nodal functions.

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Age-related differences in isolated rat sinus node function

Cited by 22 publications

References 17 publications

Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

Declining Into Failure

Gender-Related Differences in a Process of the Age-Dependent Alterations of the Elements in Monkey Sino-Atrial Node

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