Neuronal sodium channels: emerging components of the nano‐machinery of cardiac calcium cycling

Veeraraghavan, Rengasayee; Györke, Sándor; Radwański, Przemysław

doi:10.1113/jp273058

Cited by 18 publications

(28 citation statements)

References 76 publications

(94 reference statements)

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“…The sodium calcium exchanger (NCX) inextricably couples the cycling of Ca(2+) and Na(+) in cardiac myocytes. However, neuronal sodium channels are important components of the nano-machinery of cardiac calcium cycling [48]. Similarly, CaM-dependent protein kinase IIα (CaMKIIα) acts in calcium signaling mechanism in ischemic injury [49].…”

Section: Role Of Mineral Elements In Osteogenic Differentiationmentioning

confidence: 99%

Role of Calcium Bio-Minerals in Regenerative Medicine and Tissue Engineering

Upadhyay¹

2017

JSRT

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Present review article emphasize role of biominerals in regenerative medicine and tissue engineering. Among all biominerals calcium is essential for body growth and development. It also performs many fundamental functions in cellular metabolism. Inside cell organic matrix is calcified by calcium phosphate minerals. It also embeds bone cells which participate in the maintenance and organization of bone. This article also emphasizes use of hydroxyapatite a natural mineral used as a bone-building supplement with superior absorption in comparison to calcium. It also explains use of scaffolds that mimic the structure and composition of bone tissue and cells. It also signifies use of HAc microparticles or microparticles loaded with PL, superparamagnetic iron oxide nanoparticles, composite scaffolds of nano-hydroxyapatite (nHAp) and silk fibroin (SF) in bone regeneration mainly in osteoregenerative therapy. For better and successful bone regeneration there is a need to develop low cost sintered hydroxyfluorapatite discs to support cellular proliferation and colonization, tailored mineralization, cell and drug delivery. All adhesion components should show low immunoreactivity and high biocompatibility with natural bone tissues. There is an essential need to make new biocompatible materials for scaffolding, biomeinerals and cementing formulations for regeneration of bones, craniomaxillofacial, dental and orthopedic surgery.

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Section: Role Of Mineral Elements In Osteogenic Differentiationmentioning

confidence: 99%

Role of Calcium Bio-Minerals in Regenerative Medicine and Tissue Engineering

Upadhyay¹

2017

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“…Interestingly, however, emerging research is identifying neuronal sodium channel isoforms as previously unanticipated, albeit functionally key, components of calcium cycling nanodomains at the dyadic cleft (Veeraraghavan et al . ). Thus, the functional implications of nanodomain organization – ion channel clustering and ultrastructure – extend well beyond the role of ephaptic coupling in cardiac conduction.…”

Section: Ephaptic Coupling In the Heartmentioning

confidence: 97%

Sodium channel clusters: harmonizing the cardiac conduction orchestra

Veeraraghavan

Radwański

2018

The Journal of Physiology

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“…Since then, multiple groups have provided evidence for co-compartmentation of Na + and Ca 2+ handling proteins within dyadic nanodomains ( Scriven et al, 2000 ; Jayasinghe et al, 2009 ). In recent years, evidence has mounted that the high gain system of cardiac Ca 2+ cycling is tightly regulated by nNa V s, and NCX localized within the cleft ( Radwański and Poelzing, 2011 ; Radwański et al, 2013 , 2015 , 2016 ; Veeraraghavan et al, 2017 ). However, the molecular stoichiometry of Na + /Ca 2+ handling machinery (NCX, RyR, Na V s) and inter-species differences remain to be elucidated.…”

Section: The Nano-machinery Of Cardiac Excitation-contraction Couplinmentioning

confidence: 99%

Cardiac Arrhythmias as Manifestations of Nanopathies: An Emerging View

et al. 2018

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A nanodomain is a collection of proteins localized within a specialized, nanoscale structural environment, which can serve as the functional unit of macroscopic physiologic processes. We are beginning to recognize the key roles of cardiomyocyte nanodomains in essential processes of cardiac physiology such as electrical impulse propagation and excitation–contraction coupling (ECC). There is growing appreciation of nanodomain dysfunction, i.e., nanopathy, as a mechanistic driver of life-threatening arrhythmias in a variety of pathologies. Here, we offer an overview of current research on the role of nanodomains in cardiac physiology with particular emphasis on: (1) sodium channel-rich nanodomains within the intercalated disk that participate in cell-to-cell electrical coupling and (2) dyadic nanodomains located along transverse tubules that participate in ECC. The beat to beat function of cardiomyocytes involves three phases: the action potential, the calcium transient, and mechanical contraction/relaxation. In all these phases, cell-wide function results from the aggregation of the stochastic function of individual proteins. While it has long been known that proteins that exist in close proximity influence each other’s function, it is increasingly appreciated that there exist nanoscale structures that act as functional units of cardiac biophysical phenomena. Termed nanodomains, these structures are collections of proteins, localized within specialized nanoscale structural environments. The nano-environments enable the generation of localized electrical and/or chemical gradients, thereby conferring unique functional properties to these units. Thus, the function of a nanodomain is determined by its protein constituents as well as their local structural environment, adding an additional layer of complexity to cardiac biology and biophysics. However, with the emergence of experimental techniques that allow direct investigation of structure and function at the nanoscale, our understanding of cardiac physiology and pathophysiology at these scales is rapidly advancing. Here, we will discuss the structure and functions of multiple cardiomyocyte nanodomains, and novel strategies that target them for the treatment of cardiac arrhythmias.

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Neuronal sodium channels: emerging components of the nano‐machinery of cardiac calcium cycling

Cited by 18 publications

References 76 publications

Role of Calcium Bio-Minerals in Regenerative Medicine and Tissue Engineering

Role of Calcium Bio-Minerals in Regenerative Medicine and Tissue Engineering

Sodium channel clusters: harmonizing the cardiac conduction orchestra

Cardiac Arrhythmias as Manifestations of Nanopathies: An Emerging View

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