Effects of changes in frequency on guinea pig ventricular action potential duration and on QT interval under different experimental conditions

In the heart, the delayed rectifier K current, IK, composed of the rapid (IKr) and slow (IKs) components contributes prominently to normal cardiac repolarization. In lipotoxicity, chronic elevation of pro-inflammatory cytokines may remodel IK, elevating the risk for ventricular arrythmias and sudden cardiac death. We investigated whether and how the pro-inflammatory interleukin-6 altered IK in the heart, using electrophysiology to evaluate changes in IK in adult guinea pig ventricular myocytes. We found that palmitic acid (a potent inducer of lipotoxicity), induced a rapid (~24 h) and significant increase in IL-6 in RAW264.7 cells. PA-diet fed guinea pigs displayed a severely prolonged QT interval when compared to low-fat diet fed controls. Exposure to isoproterenol induced torsade de pointes, and ventricular fibrillation in lipotoxic guinea pigs. Pre-exposure to IL-6 with the soluble IL-6 receptor produced a profound depression of IKr and IKs densities, prolonged action potential duration, and impaired mitochondrial ATP production. Only with the inhibition of IKr did a proarrhythmic phenotype of IKs depression emerge, manifested as a further prolongation of action potential duration and QT interval. Our data offer unique mechanistic insights with implications for pathological QT interval in patients and vulnerability to fatal arrhythmias.

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Opposite effects of halothane on guinea-pig ventricular action potential duration

European Journal of Pharmacology ◽

10.1016/s0014-2999(00)00019-4 ◽

2000 ◽

Vol 390 (1-2) ◽

pp. 95-101 ◽

Cited By ~ 4

Author(s):

Cécile Terrenoire ◽

Vincent Piriou ◽

Robert Bonvallet ◽

Christophe Chouabe ◽

Leon Espinosa ◽

...

Keyword(s):

Guinea Pig ◽

Action Potential ◽

Action Potential Duration ◽

Ventricular Action Potential

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Dual effects of external magnesium on action potential duration in guinea pig ventricular myocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.6.h2321 ◽

1995 ◽

Vol 268 (6) ◽

pp. H2321-H2328 ◽

Cited By ~ 3

Author(s):

S. Zhang ◽

T. Sawanobori ◽

H. Adaniya ◽

Y. Hirano ◽

M. Hiraoka

Keyword(s):

Guinea Pig ◽

Action Potential ◽

Decay Time ◽

Action Potential Duration ◽

Time Course ◽

Ventricular Myocytes ◽

Membrane Surface ◽

Surface Charges ◽

Whole Cell Patch Clamp ◽

K Current

Effects of extracellular magnesium (Mg2+) on action potential duration (APD) and underlying membrane currents in guinea pig ventricular myocytes were studied by using the whole cell patch-clamp method. Increasing external Mg2+ concentration [Mg2+]o) from 0.5 to 3 mM produced a prolongation of APD at 90% repolarization (APD90), whereas 5 and 10 mM Mg2+ shortened it. [Mg2+]o, at 3 mM or higher, suppressed the delayed outward K+ current and the inward rectifier K+ current. Increases in [Mg2+]o depressed the peak amplitude and delayed the decay time course of the Ca2+ current (ICa), the latter effect is probably due to the decrease in Ca(2+)-induced inactivation. Thus 3 mM Mg2+ suppressed the peak ICa but increased the late ICa amplitude at the end of a 200-ms depolarization pulse, whereas 10 mM Mg2+ suppressed both components. Application of 10 mM Mg2+ shifted the voltage-dependent activation and inactivation by approximately 10 mV to more positive voltage due to screening the membrane surface charges. Application of manganese (1-5 mM) also caused dual effects on APD90, similar to those of Mg2+, and suppressed the peak ICa with slowed decay. These results suggest that the dual effects of Mg2+ on APD in guinea pig ventricular myocytes can be, at least in part, explained by its action on ICa with slowed decay time course in addition to suppressive effects on K+ currents.

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