From channels to systems: Ca<sup>2+</sup>‐sensitive K<sup>+</sup> currents, alternans and cardiac arrhythmia

Huang, Christopher

doi:10.1113/jp273815

Cited by 4 publications

(4 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies performed by Badisa et al [ 24 ] suggested that the cell types examined are more inclined to withstand greater cocaine concertation, however, the present investigation indicates cardiomyocytes are more sensitive to higher cocaine concentration exposures. This finding corroborates Wu et al [ 16 ], which demonstrated cocaine concentrations between 1–100 µM abrogate potassium channel activity which in turn alters functional regulation of cardiac cells associated with cardiac arrhythmias, a known implication of cocaine induced cardiac dysregulation [ 11 , 30 ]. SEM analysis indicated that treatments at 50 µg/mL cocaine enhanced the formation of cell periphery and surface blebbing with significant reductions in cellular outgrowths and concomitant loss of spindle-to-satellite architecture.…”

Section: Discussionsupporting

confidence: 89%

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Verma

Merve

Remeškevičius

et al. 2021

IJMS

View full text Add to dashboard Cite

Cocaine is one of the most widely abused illicit drugs worldwide and has long been recognised as an agent of cardiac dysfunction in numerous cases of drug overdose. Cocaine has previously been shown to up-regulate cytoskeletal rearrangements and morphological changes in numerous tissues; however, previous literature observes such changes primarily in clinical case reports and addiction studies. An investigation into the fundamental cytoskeletal parameters of migration, adhesion and proliferation were studied to determine the cytoskeletal and cytotoxic basis of cocaine in cardiac cells. Treatment of cardiac myocytes with cocaine increased cell migration and adhesion (p < 0.05), with no effect on cell proliferation, except with higher doses eliciting (1–10 μg/mL) its diminution and increase in cell death. Cocaine downregulated phosphorylation of cofilin, decreased expression of adhesion modulators (integrin-β3) and increased expression of ezirin within three hours of 1 μg/mL treatments. These functional responses were associated with changes in cellular morphology, including alterations in membrane stability and a stellate-like phenotype with less compaction between cells. Higher dose treatments of cocaine (5–10 μg/mL) were associated with significant cardiomyocyte cell death (p < 0.05) and loss of cellular architecture. These results highlight the importance of cocaine in mediating cardiomyocyte function and cytotoxicity associated with the possible loss of intercellular contacts required to maintain normal cell viability, with implications for cardiotoxicity relating to hypertrophy and fibrogenesis.

show abstract

Section: Discussionsupporting

confidence: 89%

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Verma

Merve

Remeškevičius

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Unity gradients in the derived λ(λ 0 ) plots (iii; dashed tangent) yield instability conditions that additionally incorporate AP propagation contributions. (c and d adapted from [ 38 ]).…”

Section: Methodsmentioning

confidence: 99%

Cardiac electrophysiological adaptations in the equine athlete—Restitution analysis of electrocardiographic features

Chadda

Matthews

et al. 2018

PLoS ONE

Self Cite

View full text Add to dashboard Cite

Exercising horses uniquely accommodate 7–8-fold increases in heart rate (HR). The present experiments for the first time analysed the related adaptations in action potential (AP) restitution properties recorded by in vivo telemetric electrocardiography from Thoroughbred horses. The horses were subjected to a period of acceleration from walk to canter. The QRS durations, and QT and TQ intervals yielded AP conduction velocities, AP durations (APDs) and diastolic intervals respectively. From these, indices of active, λ = QT/(QRS duration), and resting, λ0 = TQ/(QRS duration), AP wavelengths were calculated. Critical values of QT and TQ intervals, and of λ and λ0 at which plots of these respective pairs of functions showed unity slope, were obtained. These were reduced by 38.9±2.7% and 86.2±1.8%, and 34.1±3.3% and 85.9±1.2%, relative to their resting values respectively. The changes in λ were attributable to falls in QT interval rather than QRS duration. These findings both suggested large differences between the corresponding critical (129.1±10.8 or 117.4±5.6 bpm respectively) and baseline HRs (32.9±2.1 (n = 7) bpm). These restitution analyses thus separately identified concordant parameters whose adaptations ensure the wide range of HRs over which electrophysiological activation takes place in an absence of heart block or arrhythmias in equine hearts. Since the horse is amenable to this in vivo electrophysiological analysis and displays a unique wide range of heart rates, it could be a novel cardiac electrophysiology animal model for the study of sudden cardiac death in human athletes.

show abstract

“…Their findings help to disentangle the coupling of non-linear dynamic systems, and elucidate the mechanisms underlying cardiac alternans caused by changes in Ca 2+ -sensitive K + channels under pathological conditions. Their work has also been put into a larger perspective by Huang et al (2017). Devenyi et al (2017) developed a powerful dynamic-clamp approach to study the two major K + channels -I Ks and I Krthat are responsible for AP repolarization.…”

Section: Conference and White Papers On Cardiac K + Channelsmentioning

confidence: 99%

K⁺ channels and cardiac electrophysiology

Bers

Chen‐Izu

2017

The Journal of Physiology

View full text Add to dashboard Cite

From channels to systems: Ca²⁺‐sensitive K⁺ currents, alternans and cardiac arrhythmia

Cited by 4 publications

References 5 publications

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Cardiac electrophysiological adaptations in the equine athlete—Restitution analysis of electrocardiographic features

K⁺ channels and cardiac electrophysiology

Contact Info

Product

Resources

About

From channels to systems: Ca2+‐sensitive K+ currents, alternans and cardiac arrhythmia

Cited by 4 publications

References 5 publications

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Cardiac electrophysiological adaptations in the equine athlete—Restitution analysis of electrocardiographic features

K+ channels and cardiac electrophysiology

Contact Info

Product

Resources

About

From channels to systems: Ca²⁺‐sensitive K⁺ currents, alternans and cardiac arrhythmia

K⁺ channels and cardiac electrophysiology