Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

Weisbrod, David; Khun, Shiraz Haron; Bueno, H. P.; Peretz, Asher; Attali, Bernard

doi:10.1038/aps.2015.135

Cited by 34 publications

(35 citation statements)

References 191 publications

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“…Pacemaker cells are natural oscillators that cause involuntary muscles and other tissues to contract or dilate. They are spontaneously active neurons with a specialized cell membrane that allows sodium and potassium to cross and generate regular, slow action potentials (around 100 spikes per minute) [17,18]. Modulating input controls the spike frequency.…”

Section: Electroencephalogramsmentioning

confidence: 99%

Neural Flip-Flops I: Short-Term Memory

Yoder

2018

Preprint

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9The human brain is widely regarded as the most complex known object. However, without 10 details such as redundancies and other error-correcting mechanisms, the basic organization of 11 synaptic connections within the building blocks is likely to be less complex than it appears. For 12 some brain functions, the network architectures can even be quite simple. The flip-flop and 13 oscillator models proposed here are composed of two to six neurons, and their operation depends 14 only on the minimal neuron capabilities of excitation and inhibition. These networks generate 15 neural correlates of so many major phenomena of short-term memory and electroencephalography 16 in such detail that the possibility of the brain producing the phenomena with fundamentally 17 different network architectures is remote. For example, cascaded oscillators can produce the 18 periodic activity commonly known as brainwaves by enabling the state changes of many networks 19 simultaneously. (The function of such oscillator-induced synchronization in information 20 processing systems is timing error avoidance.) Then the boundary separating the alpha and beta 21 frequency bands is 22 29

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Section: Electroencephalogramsmentioning

confidence: 99%

Neural Flip-Flops I: Short-Term Memory

Yoder

2018

Preprint

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“…K Ca are activated by intracellular Ca 2+ and subsequently generate K + efflux. Recently, studies have indicated that SK4 plays an important role in the automaticity of sinus atrial node and stem cell-derived cardiomyocytes and that SK4 inhibitors significantly reduce automaticity [10,12]. Previous studies have found that SK4 was present in the atrium.…”

Section: The Expression Of P-p38 and C-fosmentioning

confidence: 99%

“…Studies have shown that SK2 and SK4 are expressed in the pulmonary veins (PVs) of dogs and rabbits [9]. A recent study also demonstrated that SK4 is expressed in the human atrium but absent in the ventricle [10].…”

Section: Introductionmentioning

confidence: 99%

SK4 calcium-activated potassium channels activated by sympathetic nerves enhances atrial fibrillation vulnerability in a canine model of acute stroke

Yang¹,

Wang²,

Xiong

et al. 2019

Preprint

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AbstractNew-onset atrial fibrillation (AF) is common in patients with acute stroke (AS). Studies have shown that intermediate-conductance KCa channels (SK4) play an important role in cardiomyocyte automaticity. The aim of this study was to investigate the effects of SK4 on AF vulnerability in dogs with AS. Eighteen dogs were randomly divided into a control group, AS group and left stellate ganglion ablation (LSGA) group. In the control group, dogs received craniotomy without right middle cerebral artery occlusion (MCAO). AS dogs were established using a cerebral ischemic model with right MCAO. LSGA dogs underwent MCAO, and LSGA was performed. Three days later, the dispersion of the effective refractory period (dERP) and AF vulnerability in the AS group were significantly increased compared with those in the control group and LSGA group. However, no significant difference in dERP and AF vulnerability was found between the control group and the LSGA group. The SK4 inhibitor (TRAM-34) completely inhibited the inducibility of AF in AS dogs. SK4 expression and levels of noradrenaline (NE), β1-AR, p38 and c-Fos in the atrium were higher in the AS dogs than in the control group or LSGA group. However, no significant difference in SK4 expression or levels of NE, β1-AR, p38 and c-Fos in the left atrium was observed between the control group and LSGA group. SK4 plays a key role in AF vulnerability in a canine model with AS. The effects of LSGA on AF vulnerability were associated with the p38 signaling pathways.

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“…After years of exploration and practice, there is still room for improvement of symptomatic treatment methods including pharmacotherapy, percutaneous catheter ablation, or pacemaker implantation (Nattel and Carlsson 2006;Carlsson et al 2010;Yamada and Kay 2012;Vernooy et al 2014). Many factors can disrupt cardiac rhythms, including myocardial ischemia, prescription drugs, electrolyte disorders, smoking, alcohol, coffee, physical exercise, mental stimulation, ion channel abnormalities, or genetic defects (Kathiresan and Srivastava 2012;Peyronnet et al 2016;Weisbrod et al 2016;Chrysant 2017;Du et al 2017;Goyal et al 2017). Undoubtedly, defects of cardiac pacemaker cells and the corresponding tissues also disrupt cardiac rhythms (Yazawa et al 2011;Vedantham 2015).…”

Section: Introductionmentioning

confidence: 99%

Shox2: The Role in Differentiation and Development of Cardiac Conduction System

Xin

Zhao

et al. 2018

Tohoku J. Exp. Med.

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The formation and conduction of electrocardiosignals and the synchronous contraction of atria and ventricles with rhythmicity are both triggered and regulated by the cardiac conduction system (CCS). Defect of this system will lead to various types of cardiac arrhythmias. In recent years, the research progress of molecular genetics and developmental biology revealed a clearer understanding of differentiation and development of the cardiac conduction system and their regulatory mechanisms. Short stature homeobox 2 (Shox2) transcription factor, encoded by Shox2 gene in the mouse, is crucial in the formation and differentiation of the sinoatrial node (SAN). Shox2 drives embryonic development processes and is widely expressed in the appendicular skeleton, palate, temporomandibular joints, and heart. Mutations of Shox2 can lead to dysembryoplasia and abnormal phenotypes, including bradycardiac arrhythmia. In this review, we provide a summary of the latest research progress on the regulatory effects of the Shox2 gene in differentiation and development processes of the cardiac conduction system, hoping to deepen the knowledge and understanding of this systematic process based on the cardiac conduction system. Overall, the Shox2 gene is intimately involved in the differentiation and development of cardiac conduction system, especially sinoatrial node. We also summarize the current information about human SHOX2. This review article provides a new direction in biological pacemaker therapies.

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Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

Cited by 34 publications

References 191 publications

Neural Flip-Flops I: Short-Term Memory

Neural Flip-Flops I: Short-Term Memory

SK4 calcium-activated potassium channels activated by sympathetic nerves enhances atrial fibrillation vulnerability in a canine model of acute stroke

Shox2: The Role in Differentiation and Development of Cardiac Conduction System

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