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Blockade myokardialer Na+-Kanäle — ein dominantes antiarrhythmisches Wirkprinzip von Diprafenon

  • M. Kohlhardt
Conference paper

Zusammenfassung

Der Erregungsprozeß ist ein biologisch weit verbreitetes Phänomen und steht an Nerv und Muskelzellen im Dienste der Informations- und Signalübermittlung. Das Arbeitsmyokard des Herzens bildet unter physiologischen Bedingungen Aktionspotentiale aus, die durch einen plötzlichen Anstieg der Na+-Permeabilität der Zellmembran hervorgerufen werden. Treibende Kraft des dadurch möglichen transmembranären Na+-Einstroms ist ein großer elektrochemischer Gradient für Na+. Dieser Na+-Einstrom in die Myokardzelle positiviert das Membranpotential und löst durch gleichzeitige Aktivierung von Ca++-Strömen mittelbar die Herzmuskelkontraktion aus. Solche transmembranären Ionenbewegungen werden durch in die Lipidmatrix der Oberflächenmembran eingebettete, integrale Proteine vermittelt. Sowohl für Na+ als auch für Ca++ stehen spezifische Kationenkanäle zur Verfügung. K+-Kanäle schließlich sorgen für einen Auswärtsstrom, der während der Plateauphase des Aktionspotentials dominant wird und die Repolarisation einleitet. Die durch die Pionierarbeiten von Neher und Sakmann Ende der 70iger Jahre entwickelte Patch-clamp-Technik (15) hat die methodischen Voraussetzungen für eine direkte biophysikalische Kanalanalyse geschaffen. Membranphysiologie und -pharmakologie sind dadurch in den letzten Jahren in eine völlig neue Dimension vorgestoßen. Vom Ionenkanal als ein vor 2 Jahrzehnten noch überwiegend spekulatives, einer direkten Messung nicht zugängliches Membranelement gelang der Sprung zur direkten Visualisierung. Die davon ausgehende Faszination beruht nicht zuletzt darauf, daß Öffnungs- und Schließungskinetik eines Ionenkanals die Reaktionskinetik wiederspiegeln, mit der das Kanalprotein von einem in einen anderen Konformationszustand übergeht.

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Copyright information

© Dr. Dietrich Steinkopff Verlag, GmbH & Co. KG, Darmstadt 1990

Authors and Affiliations

  • M. Kohlhardt
    • 1
  1. 1.Physiologisches Institut der UniversitätD-78 Freiburg/Br.Deutschland

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