scholarly journals Decreased inward rectifying K+current and increased ryanodine receptor sensitivity synergistically contribute to sustained focal arrhythmia in the intact rabbit heart

2014 ◽  
Vol 593 (6) ◽  
pp. 1479-1493 ◽  
Author(s):  
Rachel C. Myles ◽  
Lianguo Wang ◽  
Donald M. Bers ◽  
Crystal M. Ripplinger
Keyword(s):  
Ryanodine Receptor ◽  
Rabbit Heart ◽  
Receptor Sensitivity ◽  
K Current ◽  
Intact Rabbit

Effect of Cold on the Isolated and Intact Rabbit Heart

1958 ◽  
Vol 13 (3) ◽  
pp. 422-424 ◽  
Author(s):  
Benjamin G. Covino ◽  
W. R. Beavers
Keyword(s):  
Rabbit Heart ◽  
Intact Rabbit

Electrophysiologic evaluation of cardiovascular agents in the isolated intact rabbit heart

1991 ◽  
Vol 25 (3) ◽  
pp. 205-213 ◽  
Author(s):  
Scott M. Balderston ◽  
Kenneth E. Johnson ◽  
Michael J. Reiter
Keyword(s):  
Rabbit Heart ◽  
Cardiovascular Agents ◽  
Intact Rabbit

Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart

2008 ◽  
Vol 192 (3) ◽  
pp. 359-368 ◽  
Author(s):  
Cs. Lengyel ◽  
L. Virág ◽  
P. P. Kovács ◽  
A. Kristóf ◽  
P. Pacher ◽  
...  
Keyword(s):  
Rabbit Heart ◽  
Qt Prolongation ◽  
Delayed Rectifier ◽  
Diabetic Rabbit ◽  
K Current

Quinidine-induced inhibition of transient outward current in cardiac muscle

1987 ◽  
Vol 253 (3) ◽  
pp. H704-H708 ◽  
Author(s):  
Y. Imaizumi ◽  
W. R. Giles
Keyword(s):  
Action Potential ◽  
Antiarrhythmic Agent ◽  
Sodium Current ◽  
Single Cells ◽  
Outward Current ◽  
Cell Voltage ◽  
Rabbit Heart ◽  
Transient Outward Current ◽  
K Current ◽  
Therapeutic Doses

Quinidine is frequently used as a class I antiarrhythmic agent in the management of cardiac rhythm disturbances. It depresses the rapid initial depolarization of the action potential by blocking the sodium current, INa. In addition, quinidine increases the duration of the action potential and lengthens the refractory period. We have used a whole cell voltage-clamp technique to study the ionic mechanism underlying the lengthening of the action potential in single cells from the atrium and ventricle of the rabbit heart. Our data show that quinidine at therapeutic doses (3-10 microM) is a potent and selective inhibitor of a transient outward current, which controls the early repolarization of the action potential. In contrast, neither the calcium current, ICa, nor the time-independent background K+ current, IK1, is changed significantly by 10 microM quinidine. The reduction in the transient outward current can explain the lengthening of action potential and provides new insight into the mechanism of action of quinidine as an antiarrhythmic agent.

scholarly journals Role of Reduced Sarco-Endoplasmic Reticulum Ca2+-ATPase Function on Sarcoplasmic Reticulum Ca2+ Alternans in the Intact Rabbit Heart

2021 ◽  
Vol 12 ◽  
Author(s):  
Lianguo Wang ◽  
Rachel C. Myles ◽  
I-Ju Lee ◽  
Donald M. Bers ◽  
Crystal M. Ripplinger
Keyword(s):  
Endoplasmic Reticulum ◽  
Sarcoplasmic Reticulum ◽  
Optical Mapping ◽  
Cyclopiazonic Acid ◽  
Rabbit Heart ◽  
Intracellular Ca ◽  
Cardiac Alternans ◽  
Intact Rabbit ◽  
Rapid Ventricular Pacing ◽  
Serca Inhibition

Sarcoplasmic reticulum (SR) Ca2+ cycling is tightly regulated by ryanodine receptor (RyR) Ca2+ release and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) Ca2+ uptake during each excitation–contraction coupling cycle. We previously showed that RyR refractoriness plays a key role in the onset of SR Ca2+ alternans in the intact rabbit heart, which contributes to arrhythmogenic action potential duration (APD) alternans. Recent studies have also implicated impaired SERCA function, a key feature of heart failure, in cardiac alternans and arrhythmias. However, the relationship between reduced SERCA function and SR Ca2+ alternans is not well understood. Simultaneous optical mapping of transmembrane potential (Vm) and SR Ca2+ was performed in isolated rabbit hearts (n = 10) using the voltage-sensitive dye RH237 and the low-affinity Ca2+ indicator Fluo-5N-AM. Alternans was induced by rapid ventricular pacing. SERCA was inhibited with cyclopiazonic acid (CPA; 1–10 μM). SERCA inhibition (1, 5, and 10 μM of CPA) resulted in dose-dependent slowing of SR Ca2+ reuptake, with the time constant (tau) increasing from 70.8 ± 3.5 ms at baseline to 85.5 ± 6.6, 129.9 ± 20.7, and 271.3 ± 37.6 ms, respectively (p < 0.05 vs. baseline for all doses). At fast pacing frequencies, CPA significantly increased the magnitude of SR Ca2+ and APD alternans, most strongly at 10 μM (pacing cycle length = 220 ms: SR Ca2+ alternans magnitude: 57.1 ± 4.7 vs. 13.4 ± 8.9 AU; APD alternans magnitude 3.8 ± 1.9 vs. 0.2 ± 0.19 AU; p < 0.05 10 μM of CPA vs. baseline for both). SERCA inhibition also promoted the emergence of spatially discordant alternans. Notably, at all CPA doses, alternation of SR Ca2+ release occurred prior to alternation of diastolic SR Ca2+ load as pacing frequency increased. Simultaneous optical mapping of SR Ca2+ and Vm in the intact rabbit heart revealed that SERCA inhibition exacerbates pacing-induced SR Ca2+ and APD alternans magnitude, particularly at fast pacing frequencies. Importantly, SR Ca2+ release alternans always occurred before the onset of SR Ca2+ load alternans. These findings suggest that even in settings of diminished SERCA function, relative refractoriness of RyR Ca2+ release governs the onset of intracellular Ca2+ alternans.

scholarly journals Subcellular Ca2+ signaling in the heart: the role of ryanodine receptor sensitivity

2010 ◽  
Vol 136 (2) ◽  
pp. 135-142 ◽  
Author(s):  
Benjamin L. Prosser ◽  
Christopher W. Ward ◽  
W.J. Lederer
Keyword(s):  
Ryanodine Receptor ◽  
Receptor Sensitivity
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