Block of IKs, the slow component of the delayed rectifier K+ current, by the diuretic agent indapamide in guinea pig myocytes.

Turgeon, Jacques; Daleau, Pascal; Bennett, Paul B.; Wiggins, S.; Selby, Lloyd A.; Roden, Dan M.

doi:10.1161/01.res.75.5.879

Cited by 69 publications

(41 citation statements)

References 41 publications

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“…For I K4AP , the current density was 7.8 ± 6A). Effects of indapamide (an agent shown to selectively block I Ks ) [25] were also assessed with concentrations up to 100 µM, but no significant alterations of I KM3 or I K4AP were observed in any of the four cells examined (data not shown).…”

Section: Comparison Of Pharmacological Propertiesmentioning

confidence: 99%

Electrophysiological Characterization of Cardiac Muscarinic Acetylcholine Receptors: Different Subtypes Mediate Different Potassium Currents

Shi

Yang

Xu³

et al. 2003

Cell Physiol Biochem

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To characterize electrophysiologically the K⁺ currents mediated by various mAChR subtypes, we performed detailed whole-cell patch-clamp studies in canine atrial myocytes. I_KACh was induced by 1 mM ACh (acetylcholine) or by arecaidine but-2-ynyl ester tosylate (100 nM, an M₂ receptor selective agonist) and was blocked by methoctramine (20 nM, an M₂ receptor selective antagonist). Tetramethylammonium (0.5 mM) activated a K⁺ conductance with delayed rectifying properties (I_KM3) and the currents were highly sensitive to 4-diphenylacetoxy-N-methylpiperidine methiodide (2 nM, an M₃ receptor inhibitor). 4-aminopyridine (1 mM) induced a delayed rectifier-like current (I_K4AP) which was selectively suppressed by tropicamide (200 nM, an M₄ receptor blocker). The current waveforms, I-V relationships, steady-state voltage-dependence, kinetics and pharmacological properties of these three currents were different from one another and distinct from the classical delayed rectifier K⁺ currents (I_Kr and I_Ks). Both I_KACh and I_K4AP were sensitive to pertussis ntoxin, whereas I_KM3 was not. Isoproterenol (1 mM) markedly depressed I_KM3, but increased I_K4AP and did not alter I_KACh. The effects of isoproterenol were reversed by propranolol (1 mM); and ACh completely suppressed I_KM3 and I_K4AP. The results suggest that the K⁺ currents mediated by different subtypes of mAChR represent different populations of K⁺ channels and that the cholinergic regulation of the heart’s electrical function is a consequence of activating multiple mAChRs linked to different effector systems with potentially varying signal transduction.

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Section: Comparison Of Pharmacological Propertiesmentioning

confidence: 99%

Electrophysiological Characterization of Cardiac Muscarinic Acetylcholine Receptors: Different Subtypes Mediate Different Potassium Currents

Shi

Yang

Xu³

et al. 2003

Cell Physiol Biochem

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“…However, it has been found that the time-dependent delayed rectifier-like current induced by 4-AP has kineticand pharmacological-sensitive properties different from those of IK, and IKy, the delayed rectifiers described in other cardiac preparations (Sanguinetti & Jurkiewicz, 1990 (Jurkiewicz & Sanguinetti, 1993), or the IK8 blocker indapamide (Turgeon et al 1994). …”

mentioning

confidence: 98%

4‐aminopyridine activates potassium currents by activation of a muscarinic receptor in feline atrial myocytes.

Navarro‐Polanco

Sánchez-Chapula

1997

The Journal of Physiology

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1. The effects of 4-aminopyridine (4-AP) on action potentials, macroscopic membrane currents and single-channel recording from cardiac left atrial myocytes of the adult cat were studied using the whole-cell and cell-attached configurations of the patch-clamp technique. 2. 4-AP (1 mM) produced a hyperpolarization of the resting membrane potential and a shortening of action potential duration. Under voltage-clamp conditions, we have found that 4-AP increased a background current and a delayed rectifier outward current. These effects were antagonized by atropine. In addition, both effects seemed to be mediated through a pertussis toxin-sensitive G protein.3. The background current induced by 4-AP displayed properties that are highly similar to those of the inwardly rectifying potassium current activated by acetylcholine ('K(ACh)). The time-dependent potassium current activated by 4-AP has kinetic and pharmacological properties different from those of the delayed rectifier potassium current previously identified in cardiac myocytes. 4. The activation of the delayed rectifier-like potassium current could be explained by the activation of a novel muscarinic receptor subtype in which acetylcholine acts as the antagonist. Another possibility is that 4-AP activates IK(ACh) in a time-and voltagedependent manner.

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“…Recent work has shown that /KS iS selectively suppressed by the diuretic indapamide (Turgeon, Daleau, Bennett, Wiggins, Selby & Roden, 1994) and by some intravenous anaesthetic drugs (Takahashi & Terrar, 1995).…”

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confidence: 99%

Separation of the components of the delayed rectifier potassium current using selective blockers of IKr and IKs in guinea‐pig isolated ventricular myocytes

Heath¹,

Terrar²

1996

Experimental Physiology

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Delayed rectifier potassium current (IK) was investigated in guinea‐pig isolated ventricular myocytes under voltage‐clamp conditions (‘switched’ single electrode clamp), using selective blockers and/or different activation protocols to separate its rapid (IKr) and slow (IKs) components. The class III antiarrhythmic compound E4031 (5 microM) was used to block IKr and the anaesthetic drugs propofol (100 microM) or thiopentone (100 microM) to block IKs. In all experiments L‐type calcium currents were blocked with nifedipine (2 microM). Complementary effects of E4031 and the anaesthetic drugs on the components of IK were observed. The E4031‐sensitive current (IKr) resembled the current remaining in the presence of the anaesthetics and, likewise, the anaesthetic‐sensitive current (IKs) resembled the current remaining in the presence of E4031. Under the conditions of these experiments, the relative contribution of the two components to total IK tail current was found to be approximately equal after a 400 ms depolarization to +40 mV. For example, IKr was 58 +/− 10% of total IK tail current when measured as the E4031‐sensitive current, 41 +/− 6% as the propofol‐insensitive current and 43 +/− 7% as the thiopentone‐insensitive current. In the presence of both E4031 and propofol or thiopentone the IK tail current deactivating at ‐40 mV was completely eliminated, leaving a residual current during the pulse which reversed at ‐46 +/− 1 mV. To avoid complication of the ‘envelope of tails’ test with this residual current, the tail:pulse ratio was calculated for the anaesthetic‐sensitive component and this was constant, consistent with block of a single component of IK. Forskolin (1 microM) enhanced the current most consistent with IKs. Propofol (300 microM) caused a 64 +/− 3% increase in action potential duration in the presence of both E4031 (5 microM) and nifedipine (2 microM), consistent with an important role for IKs in the repolarization of the action potential in the guinea‐pig heart. The observations therefore provide further support for separate components of IK with different characteristics in the guinea‐pig heart; it appears that E4031 and propofol or thiopentone are useful complementary tools for their separation.

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Block of IKs, the slow component of the delayed rectifier K+ current, by the diuretic agent indapamide in guinea pig myocytes.

Cited by 69 publications

References 41 publications

Electrophysiological Characterization of Cardiac Muscarinic Acetylcholine Receptors: Different Subtypes Mediate Different Potassium Currents

Electrophysiological Characterization of Cardiac Muscarinic Acetylcholine Receptors: Different Subtypes Mediate Different Potassium Currents

4‐aminopyridine activates potassium currents by activation of a muscarinic receptor in feline atrial myocytes.

Separation of the components of the delayed rectifier potassium current using selective blockers of IKr and IKs in guinea‐pig isolated ventricular myocytes

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