Potassium channels in the sinoatrial node and their role in heart rate control

Aziz, Qadeer; Li, Yiwen; Tinker, Andrew

doi:10.1080/19336950.2018.1532255

Cited by 20 publications

(19 citation statements)

References 117 publications

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“…The most prominent feature was the temporary arrest of synchronous beating (Fig. 5), reminding us of the amplitude death of coupled oscillators [49][50][51] and sinus arrest of in vivo hearts [52][53][54] . Its mechanism seemed to be hidden in the momentary arrests of the CSs that appeared as its precursors.…”

Section: Discussionmentioning

confidence: 99%

Mechanical activities of self-beating cardiomyocyte aggregates under mechanical compression

Nakano

Nanri

Tsukamoto

et al. 2021

Sci Rep

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Since the discovery of synchronous pulsations in cardiomyocytes (CMs), electrical communication between CMs has been emphasized; however, recent studies suggest the possibility of mechanical communication. Here, we demonstrate that spherical self-beating CM aggregates, termed cardiac spheroids (CSs), produce enhanced mechanical energy under mechanical compression and work cooperatively via mechanical communication. For single CSs between parallel plates, compression increased both beating frequency and beating energy. Contact mechanics revealed a scaling law on the beating energy, indicating that the most intensively stressed cells in the compressed CSs predominantly contributed to the performance of mechanical work against mechanical compression. For pairs of CSs between parallel plates, compression immediately caused synchronous beating with mechanical coupling. Compression tended to strengthen and stabilize the synchronous beating, although some irregularity and temporary arrest were observed. These results suggest that mechanical compression is an indispensable control parameter when evaluating the activities of CMs and their aggregates.

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Section: Discussionmentioning

confidence: 99%

Mechanical activities of self-beating cardiomyocyte aggregates under mechanical compression

Nakano

Nanri

Tsukamoto

et al. 2021

Sci Rep

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“…Yanni et al (68) showed that in aged mice there is an increase in the area of the SAN that lacks the relatively TTX-resistant Na V 1.5 sodium channel isoform and yet an increased effect of 2 μM TTX on firing rate, possibly reflecting an upregulation of TTX-sensitive Na + channel isoforms. K + currents.-There are clear roles for voltage-gated, Ca 2+ -activated, and inward rectifier K + channels in the repolarization and diastolic depolarization phases of the SAN AP (93)(94)(95)(96)(97)(98). The delayed rectifier K + channels K V 7.1 (KCNQ1), which underlies I Ks , and K V 11.1 (ERG), which produces I Kr , are thought to be primarily responsible for repolarization of the sinoatrial AP.…”

Section: Overview Of Age-dependent Changes In Ionic Currents In Sinoatrial Node Myocytesmentioning

confidence: 99%

“…The relative lack of information about K + currents in SAMs is particularly important for aging because the AP prolongation along with reduced Ca 2+ current density predicts a decrease in K + currents in aged SAMs (10,11,13). Although, as discussed above, K + currents play an important role in determining cycle length through modulation of multiple AP waveform parameters and are implicated in SND (95,(97)(98)(99)(100)103), there is no information to our knowledge about age-dependent changes in K + currents in SAMs.…”

Section: Limitations Gaps In Knowledge and Future Directionsmentioning

confidence: 99%

Cardiac Pacemaker Activity and Aging

Peters

Sharpe

Proenza

2020

Annu. Rev. Physiol.

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A progressive decline in maximum heart rate (mHR) is a fundamental aspect of aging in humans and other mammals. This decrease in mHR is independent of gender, fitness, and lifestyle, affecting in equal measure women and men, athletes and couch potatoes, spinach eaters and fast food enthusiasts. Importantly, the decline in mHR is the major determinant of the age-dependent decline in aerobic capacity that ultimately limits functional independence for many older individuals. The gradual reduction in mHR with age reflects a slowing of the intrinsic pacemaker activity of the sinoatrial node of the heart, which results from electrical remodeling of individual pacemaker cells along with structural remodeling and a blunted β-adrenergic response. In this review, we summarize current evidence about the tissue, cellular, and molecular mechanisms that underlie the reduction in pacemaker activity with age and highlight key areas for future work.

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“…This cardiac impulse in the SAN is initially mediated by a sodium influx via hyperpolarization-activated cyclic nucleotide-gated cation channels (HCN1, 2, and 4). Thereafter, depolarization occurs progressively via T-type calcium channels (Cav3.1 and 3.2), and L-type calcium channels (Cav1.2 and 1.3) 2,3 . Repolarization of the cardiac action potential occurs via the inactivation of L-type calcium currents and the opening of potassium channels, such as IKr (Kv11.1/hERG) and IKs (KCNQ1/KvLQT1) in the SAN.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to these key ion channels, the messenger RNA (mRNA) expression levels of acetylcholine-activated K+ current, IKACh (Kir3.1 and 3.4), and sodium-calcium exchanger 1 (NCX1) are also known to regulate the cardiac action potential 3 .…”

Section: Introductionmentioning

confidence: 99%

Ion channel mRNA distribution and expression in the sinoatrial node and right atrium of dogs and monkeys

2021

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There are limited data on the gene expression profiles of ion channels in the sinoatrial node (SAN) of dogs and monkeys. In this study, the messenger RNA (mRNA) expression profiles of various ion channels in the SAN of naïve dogs and monkeys were examined using RNAscope ○ R in situ hybridization and compared with those in the surrounding right atrium (RA) of each species.Regional-specific Cav1.3 and HCN4 expression was observed in the SAN of dogs and monkeys.Additionally, HCN1 in dogs was only expressed in the SAN group. The expression profiles of Cav3.1 and Cav3.2 in the SAN and RA were completely different between dogs and monkeys. Dog hearts only expressed Cav3.2; however, Cav3.1 was detected only in monkeys, and the expression score in the SAN was slightly higher than that in the RA. Although Kir3.1 and NCX1 in dogs were equally expressed in both the SAN and RA, the expression scores of these genes in the SAN of monkeys were slightly higher than those in the RA. The Kir3.4 expression score in the SAN of dogs and monkeys was also slightly higher than that in the RA. The mRNA expression scores of Kv11.1/ERG and KvLQT1 were equally observed in both the SAN and RA of dogs and monkeys. HCN2 was not detected in dogs and monkeys.In summary, we used RNAscope to demonstrate the SAN-specific gene expression patterns of ion channels, which may be useful in explaining the effect of pacemaking and/or hemodynamic effects in nonclinical studies.

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Potassium channels in the sinoatrial node and their role in heart rate control

Cited by 20 publications

References 117 publications

Mechanical activities of self-beating cardiomyocyte aggregates under mechanical compression

Mechanical activities of self-beating cardiomyocyte aggregates under mechanical compression

Cardiac Pacemaker Activity and Aging

Ion channel mRNA distribution and expression in the sinoatrial node and right atrium of dogs and monkeys

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