Norepinephrine induces action potential prolongation and early afterdepolarizations in ventricular myocytes isolated from human end-stage failing hearts

Veldkamp, Marieke W.; Verkerk, Arie O.; Ginneken, A. C. G. Van; Baartscheer, Antonius; Schumacher, Christian; Jonge, N. De; Bakker, Jacques M.T. de; Opthof, T.

doi:10.1053/euhj.2000.2499

Cited by 63 publications

(43 citation statements)

References 43 publications

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“…In mammals, adrenergic stimulation can either increase or decrease APD [55][56][57]. The prolongation of APD with AD in mammals is often attributed to an increase in I Ca and the greater influx of Ca 2þ on the Ca 2þ -window current [58]. We show AD increases I Ca in bluefin tuna myocytes (figure 4) and increases the amplitude of the I Ca window current (figure 5), especially at cold temperatures when the APD is significantly prolonged.…”

Section: Discussionmentioning

confidence: 86%

Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving

2015

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Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation-contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 288C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca 2þ transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation-contraction coupling across an acute 208C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range.

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Section: Discussionmentioning

confidence: 86%

Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving

2015

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“…Consistent with the laborious isolation method for human ventricular cells, 11) the percentage of viable VMs was typically low (< 5%). Nevertheless, the obtained Ca 2+ -tolerant VMs were rod-shaped cells with clear cross striations, had smooth surfaces and were quiescent, even more than 8 hours after isolation.…”

Section: Methodsmentioning

confidence: 86%

“…Left midmyocardial VMs were enzymatically dissociated using coronary artery perfusion methods 11) and superfused with solution (36 ± 0.5°C) containing (mM): NaCl 140, KCl 5.4, CaCl 2 1.8, MgCl 2 1.0, glucose 5.5, HEPES 5.0, at pH 7.4 (NaOH). Consistent with the laborious isolation method for human ventricular cells, 11) the percentage of viable VMs was typically low (< 5%).…”

Section: Methodsmentioning

confidence: 99%

“…The L-type calcium current (I Ca,L ), the quasi-steady state current (I QSS ), and the transient outward potassium current (I to ) were determined by the voltage clamp protocols shown in Figure 2 and described previously. 11,12) I Ca,L amplitude was calculated as the difference between peak inward current and I QSS . I QSS amplitude was defined as the absolute current amplitude at 500ms after the onset of the voltage step.…”

Section: Methodsmentioning

confidence: 99%

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Gender Disparities in Cardiac Cellular Electrophysiology and Arrhythmia Susceptibility in Human Failing Ventricular Myocytes

et al. 2005

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SUMMARYGender disparities in ECG variables and susceptibility to arrhythmia exist. The basis of these sex-related distinctions in cardiac electrophysiology has been extensively studied in various species, but is virtually unexplored in humans. The aim of this study was to clarify the cellular basis of electrophysiological gender disparities in human cardiac myocytes.Human midmyocardial left ventricular myocytes were isolated from explanted hearts of male and female patients in end-stage heart failure at the time of cardiac transplantation. The action potentials, sarcolemmal ion currents, and susceptibility to the generation of early afterdepolarizations were studied using whole-cell patch-clamp methodology. The functional effects of gender disparities in sarcolemmal ion currents were assessed by computer simulations using the Priebe-Beuckelmann or the ten Tusscher-Noble-Noble-Panfilov human ventricular cell models.Female myocytes had significantly longer action potentials and greater susceptibility to early afterdepolarizations than male myocytes. All other action potential parameters (resting membrane potential, amplitude, plateau level, upstroke velocity, maximal velocity of phase-1 and phase-3 repolarization) had similar values for both genders. In female myocytes, the transient outward potassium current (I to1 ) tended to be smaller, while the Ltype calcium current (I Ca,L ) and quasi-steady state current (I QSS ) tended to be larger. Computer simulations showed that these subtle differences in sarcolemmal ion currents may conspire to cause the observed gender disparities in action potential properties.Female failing myocytes have longer action potentials and a greater susceptibility to early afterdepolarizations than male failing myocytes. These gender disparities may be due to slightly larger depolarizing I Ca,L in conjunction with slightly smaller repolarizing I QSS and I to1 in female myocytes. (Int Heart J 2005; 46: 1105-1118

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“…Esses neuro-hormônios podem exacerbar as anormalidades metabólicas, ocasionando, por exemplo, o aparecimento de arritmias cardíacas (9). Por esses mecanismos, a ativação neuro-hormonal contribui de maneira significativa para os sintomas relacionados à insuficiência cardíaca, assim como para a alta mortalidade dos portadores dessa doença.…”

Section: A Insuficiência Cardíacaunclassified

Efeitos da associação entre treinamento físico e tratamento farmacológico com -bloqueadores sobre a cardiomiopatia induzida por hiperatividade simpática em camundongos

Vanzelli¹

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AgradecimentosAos meus pais, Nilson Izildo Vanzelli e Maria Cristina Somolanji Vanzelli, pela educação que deram, pelo ensino dos valores, formação de caráter, apoio, confiança e compreensão. Mãe e Pai, obrigada por compensar, pequenas ausências ao meu filho, com amor, obrigada por terem sido os alicerces da minha construção. Se não fosse por vocês, com certeza, hoje não teria alcançado esse sonho.A meus irmãos, Diego Somolanji Vanzelli e Amanda Somolanji Vanzelli pelo companheirismo, apoio e amizade.Ao meu filho Daniel Vanzelli Suarez e meu sobrinho, Lucas Jackubauskas Vanzelli, por sua presença constante, seu amor, seu carinho e sua inocência.Agradeço a Stéphano Freitas Soares de Melo, pela sua sensibilidade, carinho e sua doçura. Obrigada pela sua compreensão, seu respeito, sua cumplicidade e apoio. Sem você tudo seria mais difícil.A Francisco Navarro, que jamais poderia ser esquecido nesta etapa da minha vida. Obrigada pelo apoio e incentivo na iniciação da minha vida científica e pessoal e pela confiança na minha vida acadêmica.Às minhas amigas de hoje e sempre, Aline Villa Nova Bacurau e Elenice Alves da Silva Pereira de Oliveira, por sua amizade sincera, sua dedicação, seus créditos pessoais e profissionais e seus abraços apertados. Agradeço também a Professora Tais Tinucci pela colaboração sempre disposta e bem-humorada a este trabalho e a minha vida acadêmica.Ao Professor Antonio Carlos Pereira Barretto por sua colaboração inicial ao estudo e incorporação das idéias num contexto clínico.À FAPESP pelo auxilio financeiro. E finalmente, nunca poderia deixar agradecer a Patricia Chakur Brum, que jamais poderia ser considerada apenas minha orientadora. Muito obrigada, do fundo do coração pelas inúmeras vezes que me apoiou nos momentos difíceis da minha vida pessoal, oferecendo seu carinho e sua amizade, foi compreensiva, humana, mas ao mesmo tempo firme o que me fez enxergar e aprender muitas coisas de ordem pessoal e profissional. Sou muito grata e fico muito orgulhosa por ter sido sua aluna e ter recebido sua atenção e carinho.

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Norepinephrine induces action potential prolongation and early afterdepolarizations in ventricular myocytes isolated from human end-stage failing hearts

Cited by 63 publications

References 43 publications

Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving

Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving

Gender Disparities in Cardiac Cellular Electrophysiology and Arrhythmia Susceptibility in Human Failing Ventricular Myocytes

Efeitos da associação entre treinamento físico e tratamento farmacológico com -bloqueadores sobre a cardiomiopatia induzida por hiperatividade simpática em camundongos

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