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Rapid and MR-Independent IK1 Activation by Aldosterone during Ischemia-Reperfusion.

Alexandre J, Hof T, Puddu PE, Rouet R, Guinamard R, Manrique A, Beygui F, Sallé L, Milliez P - PLoS ONE (2015)

Bottom Line: Conversely, potassium canrenoate 100 nmol/L and RU 28318 1 μmol/l alone did not affect AP parameters and premature ventricular contractions occurrence (except Vmax which was decreased by potassium canrenoate during simulated-ischemia).These deleterious effects persisted in presence of RU 28318, a specific MR antagonist, and were successfully prevented by potassium canrenoate, a non specific MR antagonist, in both microelectrode and patch-clamp recordings, thus indicating a MR-independent IK1 activation.In this ischemia-reperfusion context, aldosterone induced rapid and MR-independent deleterious effects including an arrhythmia substrate (increased APD90 dispersion) and triggered activities (increased premature ventricular contractions occurrence on reperfusion) possibly related to direct IK1 activation.

View Article: PubMed Central - PubMed

Affiliation: CHU de Caen, Department of Cardiology, Caen, France; Université de Caen Basse-Normandie, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen, France.

ABSTRACT
In ST elevation myocardial infarction (STEMI) context, clinical studies have shown the deleterious effect of high aldosterone levels on ventricular arrhythmia occurrence and cardiac mortality. Previous in vitro reports showed that during ischemia-reperfusion, aldosterone modulates K+ currents involved in the holding of the resting membrane potential (RMP). The aim of this study was to assess the electrophysiological impact of aldosterone on IK1 current during myocardial ischemia-reperfusion. We used an in vitro model of "border zone" using right rabbit ventricle and standard microelectrode technique followed by cell-attached recordings from freshly isolated rabbit ventricular cardiomyocytes. In microelectrode experiments, aldosterone (10 and 100 nmol/L, n=7 respectively) increased the action potential duration (APD) dispersion at 90% between ischemic and normoxic zones (from 95±4 ms to 116±6 ms and 127±5 ms respectively, P<0.05) and reperfusion-induced sustained premature ventricular contractions occurrence (from 2/12 to 5/7 preparations, P<0.05). Conversely, potassium canrenoate 100 nmol/L and RU 28318 1 μmol/l alone did not affect AP parameters and premature ventricular contractions occurrence (except Vmax which was decreased by potassium canrenoate during simulated-ischemia). Furthermore, aldosterone induced a RMP hyperpolarization, evoking an implication of a K+ current involved in the holding of the RMP. Cell-attached recordings showed that aldosterone 10 nmol/L quickly activated (within 6.2±0.4 min) a 30 pS K+-selective current, inward rectifier, with pharmacological and biophysical properties consistent with the IK1 current (NPo =1.9±0.4 in control vs NPo=3.0±0.4, n=10, P<0.05). These deleterious effects persisted in presence of RU 28318, a specific MR antagonist, and were successfully prevented by potassium canrenoate, a non specific MR antagonist, in both microelectrode and patch-clamp recordings, thus indicating a MR-independent IK1 activation. In this ischemia-reperfusion context, aldosterone induced rapid and MR-independent deleterious effects including an arrhythmia substrate (increased APD90 dispersion) and triggered activities (increased premature ventricular contractions occurrence on reperfusion) possibly related to direct IK1 activation.

No MeSH data available.


Related in: MedlinePlus

Representative AP recordings.Representative AP recordings obtained simultaneously in NZ and AZ in control and in presence of drugs, in same cell, in initial conditions (before initiation of ischemia and drug superfusion, left), at the end of simulated ischemia (at 30 minutes of experiment, middle) and at the end of reperfusion (at 60 minutes of experiment, right). APD90 dispersion between NZ and AZ (ΔAPD90) was measured at the end of the simulated ischemia period as APD90 NZ- APD90 AZ and is expressed as mean±SEM. Comparisons were made between control group and pharmacological groups. * P<0.05 vs controls.
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pone.0132592.g002: Representative AP recordings.Representative AP recordings obtained simultaneously in NZ and AZ in control and in presence of drugs, in same cell, in initial conditions (before initiation of ischemia and drug superfusion, left), at the end of simulated ischemia (at 30 minutes of experiment, middle) and at the end of reperfusion (at 60 minutes of experiment, right). APD90 dispersion between NZ and AZ (ΔAPD90) was measured at the end of the simulated ischemia period as APD90 NZ- APD90 AZ and is expressed as mean±SEM. Comparisons were made between control group and pharmacological groups. * P<0.05 vs controls.

Mentions: At baseline, in normal conditions, there was no significant APD90 dispersion between the two regions in all groups (Fig 2). Ischemic-like superfusion induced a significant increase in APD90 dispersion (P<0.0001) in all groups. APD90 dispersion was significantly increased by aldosterone 10 and 100 nmol/L (from 95±4 ms to 116±6 ms and 127±5 ms respectively, P<0.05). This increase of APD90 dispersion induced by aldosterone 10 nmol/L was prevented by adding potassium canrenoate 100 nmol/L but not by RU 28318 (respectively 86±3 ms and 112±5 ms vs 117±5 ms for aldosterone 10 nmol/L, P<0.05). Potassium canrenoate 100 nmol/L and RU 28318 1 μmol/L alone did not significantly affect APD90 dispersion.


Rapid and MR-Independent IK1 Activation by Aldosterone during Ischemia-Reperfusion.

Alexandre J, Hof T, Puddu PE, Rouet R, Guinamard R, Manrique A, Beygui F, Sallé L, Milliez P - PLoS ONE (2015)

Representative AP recordings.Representative AP recordings obtained simultaneously in NZ and AZ in control and in presence of drugs, in same cell, in initial conditions (before initiation of ischemia and drug superfusion, left), at the end of simulated ischemia (at 30 minutes of experiment, middle) and at the end of reperfusion (at 60 minutes of experiment, right). APD90 dispersion between NZ and AZ (ΔAPD90) was measured at the end of the simulated ischemia period as APD90 NZ- APD90 AZ and is expressed as mean±SEM. Comparisons were made between control group and pharmacological groups. * P<0.05 vs controls.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4519293&req=5

pone.0132592.g002: Representative AP recordings.Representative AP recordings obtained simultaneously in NZ and AZ in control and in presence of drugs, in same cell, in initial conditions (before initiation of ischemia and drug superfusion, left), at the end of simulated ischemia (at 30 minutes of experiment, middle) and at the end of reperfusion (at 60 minutes of experiment, right). APD90 dispersion between NZ and AZ (ΔAPD90) was measured at the end of the simulated ischemia period as APD90 NZ- APD90 AZ and is expressed as mean±SEM. Comparisons were made between control group and pharmacological groups. * P<0.05 vs controls.
Mentions: At baseline, in normal conditions, there was no significant APD90 dispersion between the two regions in all groups (Fig 2). Ischemic-like superfusion induced a significant increase in APD90 dispersion (P<0.0001) in all groups. APD90 dispersion was significantly increased by aldosterone 10 and 100 nmol/L (from 95±4 ms to 116±6 ms and 127±5 ms respectively, P<0.05). This increase of APD90 dispersion induced by aldosterone 10 nmol/L was prevented by adding potassium canrenoate 100 nmol/L but not by RU 28318 (respectively 86±3 ms and 112±5 ms vs 117±5 ms for aldosterone 10 nmol/L, P<0.05). Potassium canrenoate 100 nmol/L and RU 28318 1 μmol/L alone did not significantly affect APD90 dispersion.

Bottom Line: Conversely, potassium canrenoate 100 nmol/L and RU 28318 1 μmol/l alone did not affect AP parameters and premature ventricular contractions occurrence (except Vmax which was decreased by potassium canrenoate during simulated-ischemia).These deleterious effects persisted in presence of RU 28318, a specific MR antagonist, and were successfully prevented by potassium canrenoate, a non specific MR antagonist, in both microelectrode and patch-clamp recordings, thus indicating a MR-independent IK1 activation.In this ischemia-reperfusion context, aldosterone induced rapid and MR-independent deleterious effects including an arrhythmia substrate (increased APD90 dispersion) and triggered activities (increased premature ventricular contractions occurrence on reperfusion) possibly related to direct IK1 activation.

View Article: PubMed Central - PubMed

Affiliation: CHU de Caen, Department of Cardiology, Caen, France; Université de Caen Basse-Normandie, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen, France.

ABSTRACT
In ST elevation myocardial infarction (STEMI) context, clinical studies have shown the deleterious effect of high aldosterone levels on ventricular arrhythmia occurrence and cardiac mortality. Previous in vitro reports showed that during ischemia-reperfusion, aldosterone modulates K+ currents involved in the holding of the resting membrane potential (RMP). The aim of this study was to assess the electrophysiological impact of aldosterone on IK1 current during myocardial ischemia-reperfusion. We used an in vitro model of "border zone" using right rabbit ventricle and standard microelectrode technique followed by cell-attached recordings from freshly isolated rabbit ventricular cardiomyocytes. In microelectrode experiments, aldosterone (10 and 100 nmol/L, n=7 respectively) increased the action potential duration (APD) dispersion at 90% between ischemic and normoxic zones (from 95±4 ms to 116±6 ms and 127±5 ms respectively, P<0.05) and reperfusion-induced sustained premature ventricular contractions occurrence (from 2/12 to 5/7 preparations, P<0.05). Conversely, potassium canrenoate 100 nmol/L and RU 28318 1 μmol/l alone did not affect AP parameters and premature ventricular contractions occurrence (except Vmax which was decreased by potassium canrenoate during simulated-ischemia). Furthermore, aldosterone induced a RMP hyperpolarization, evoking an implication of a K+ current involved in the holding of the RMP. Cell-attached recordings showed that aldosterone 10 nmol/L quickly activated (within 6.2±0.4 min) a 30 pS K+-selective current, inward rectifier, with pharmacological and biophysical properties consistent with the IK1 current (NPo =1.9±0.4 in control vs NPo=3.0±0.4, n=10, P<0.05). These deleterious effects persisted in presence of RU 28318, a specific MR antagonist, and were successfully prevented by potassium canrenoate, a non specific MR antagonist, in both microelectrode and patch-clamp recordings, thus indicating a MR-independent IK1 activation. In this ischemia-reperfusion context, aldosterone induced rapid and MR-independent deleterious effects including an arrhythmia substrate (increased APD90 dispersion) and triggered activities (increased premature ventricular contractions occurrence on reperfusion) possibly related to direct IK1 activation.

No MeSH data available.


Related in: MedlinePlus