What question did this study set out to answer?

To determine whether L-type calcium currents or intracellular calcium waves predominantly drive the generation of early afterdepolarizations in ventricular cardiomyocytes under different pathological states.

February 4, 2012AJP Heart and Circulatory PhysiologyOpen Access

Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents?

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Population

Isolated ventricular myocytes from adult New Zealand White rabbits (2-3 kg).

Comparison

Pharmacological induction of early… vs Comparison between the two pharmacological…

Design

Preclinical

Authors

ZZZhenghang ZhaoXi'an Jiaotong University HWHairuo WenNational Medical Products Administration NFNadezhda FefelovaRutgers, The State University of New Jersey

Discussion

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Implication

Preclinical distinction of EAD triggers by stress type does not yet guide therapy; leaves open whether I_Ca,L or Ca-wave targeting should differ by etiology.

Key Points

To determine whether L-type calcium currents or intracellular calcium waves predominantly drive the generation of early afterdepolarizations in ventricular cardiomyocytes under different pathological states.
Simultaneously recorded action potentials and intracellular calcium images in isolated rabbit ventricular myocytes.
Evaluated early afterdepolarizations under oxidative stress induced by 200 μM hydrogen peroxide versus calcium overload induced by 100 nM isoproterenol and 50 nM BayK 8644.
Tested rate dependency, ionic channel blockers, and action potential clamp transitions from current clamp to voltage clamp.
Switching to action potential voltage clamp abolished calcium waves in the hydrogen peroxide model but allowed calcium waves to persist in the isoproterenol plus BayK 8644 model.
Reactivation of L-type calcium currents predominantly mediated early afterdepolarization generation during oxidative stress, whereas spontaneous calcium waves served as the primary cause during calcium overload.

Structured PICO

Population

Isolated ventricular myocytes from adult New Zealand White rabbits (2-3 kg).

Intervention

Pharmacological induction of early afterdepolarizations (EADs) using either hydrogen peroxide (H2O2; 200 μM) or isoproterenol (100 nM) + BayK 8644 (50 nM).

Comparator

Comparison between the two pharmacological models and control conditions.

Outcome

Mechanism of EAD genesis, specifically the relative contribution of Ca2+ waves vs. L-type Ca current (I_Ca,L), assessed via simultaneous recording of action potentials and intracellular Ca2+ images.surrogate

Reactivation of L-type calcium current plays a predominant role in EAD genesis under oxidative stress, whereas spontaneous calcium waves are the primary cause under calcium overload conditions.

Cite This Study

Zhao et al. (2012) studied this question.

synapsesocial.com/papers/6a7f609b877b9f3110f209e2 https://doi.org/10.1152/ajpheart.00742.2011

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Implication

Preclinical distinction of EAD triggers by stress type does not yet guide therapy; leaves open whether I_Ca,L or Ca-wave targeting should differ by etiology.

Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents?

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents?

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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