| Title | Effects of the chromanol HMR 1556 on potassium currents in atrial myocytes. | | Author(s) | Bosch RF, Schneck AC, Csillag S, Eigenberger B, Gerlach U, Brendel J, Lang HJ, Mewis C, Gögelein H, Seipel L, Kühlkamp V | | Institution | Abteilung III, Medizinische Klinik, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany. ralph.bosch@uni-tuebingen.de | | Source | Naunyn Schmiedebergs Arch Pharmacol 2003 Mar; 367(3):281-8. | | MeSH | Aged
Animals
Cells, Cultured
Chromans
Comparative Study
Delayed Rectifier Potassium Channels
Female
Guinea Pigs
Heart Atria
Humans
Male
Middle Aged
Myocytes, Cardiac
Patch-Clamp Techniques
Potassium Channel Blockers
Potassium Channels
Potassium Channels, Inwardly Rectifying
Potassium Channels, Voltage-Gated
Research Support, Non-U.S. Gov't
Sulfonamides
| | Abstract | PURPOSE: The chromanol HMR 1556 is a potent blocker of KvLQT1/minK potassium channels expressed in Xenopus oocytes. The compound is therefore a new class III antiarrhythmic drug with a distinct mechanism of action. However, the effect of HMR 1556 on atrial ion channels and the selectivity of block in the human heart has not been investigated. We tested the effects of HMR 1556 on repolarizing potassium currents in human and guinea pig atrial myocytes.
METHODS AND RESULTS: Single atrial myocytes were isolated by enzymatic dissociation. Atrial potassium currents (I(Ks), I(Kr), in guinea pig, I(to), I(Kur), I(K1) in humans) were recorded at 36 degrees C in the whole cell mode of the patch clamp technique. HMR 1556 produced a concentration-dependent and reversible block of I(Ks) with a half maximal concentration (EC(50)) of 6.8 nmol/l. 10 micromol/l HMR 1556 almost completely inhibited I(Ks) (97.2+/-3.2%, n=6). Steady-state activation as well as kinetic properties of the current were not altered by HMR 1556. I(Kr) currents were not affected up to concentrations of 10 micromol/l. HMR 1556 did not inhibit other potassium currents in human atrium: I(to), I(Kur) and the classical inward rectifier potassium current I(K1) were not significantly affected up to concentrations that completely blocked I(Ks) (10 micromol/l).
CONCLUSIONS: HMR 1556 is a highly-potent blocker of I(Ks) channels without exerting effects on other potassium currents involved in atrial repolarization. Given the potential advantages of I(Ks) vs. I(Kr) blockade, the drug's new mechanism of action warrants further investigation to clarify its role as an antiarrhythmic agent. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 12644901 |
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