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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

Effects of aldosterone and aldosterone + blockers (potassium canrenoate and RU 28318) on the incidence of spontaneous premature ventricular contractions during the 30-min of simulated ischemia and the 30-min of reperfusion.Data are expressed as percentage of preparations with disturbances. * P < 0.05 vs controls. # P < 0.05 between aldosterone and aldosterone + blockers.
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pone.0132592.g003: Effects of aldosterone and aldosterone + blockers (potassium canrenoate and RU 28318) on the incidence of spontaneous premature ventricular contractions during the 30-min of simulated ischemia and the 30-min of reperfusion.Data are expressed as percentage of preparations with disturbances. * P < 0.05 vs controls. # P < 0.05 between aldosterone and aldosterone + blockers.

Mentions: At baseline, in normal conditions, spontaneous premature ventricular contractions were observed in none of the groups. Results are summarized in Table 3 and in Fig 3. During simulated ischemia period, aldosterone 10 and 100 nmol/L did not modify premature ventricular contractions occurrence.


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)

Effects of aldosterone and aldosterone + blockers (potassium canrenoate and RU 28318) on the incidence of spontaneous premature ventricular contractions during the 30-min of simulated ischemia and the 30-min of reperfusion.Data are expressed as percentage of preparations with disturbances. * P < 0.05 vs controls. # P < 0.05 between aldosterone and aldosterone + blockers.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132592.g003: Effects of aldosterone and aldosterone + blockers (potassium canrenoate and RU 28318) on the incidence of spontaneous premature ventricular contractions during the 30-min of simulated ischemia and the 30-min of reperfusion.Data are expressed as percentage of preparations with disturbances. * P < 0.05 vs controls. # P < 0.05 between aldosterone and aldosterone + blockers.
Mentions: At baseline, in normal conditions, spontaneous premature ventricular contractions were observed in none of the groups. Results are summarized in Table 3 and in Fig 3. During simulated ischemia period, aldosterone 10 and 100 nmol/L did not modify premature ventricular contractions occurrence.

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