An outward current of unknown nature increases significantly when cardiac cells are treated with cyanide or subjected to hypoxia, and decreases on intracellular injection of ATP. We report here that application of the patch-clamp technique to CN-treated mammalian heart cells reveals specific K+ channels which are depressed by intracellular ATP (ATPi) at levels greater than 1 mM. For these channels, conductance in the outward direction is much larger than the inward rectifier K+ channel which is insensitive to ATP. AMP had no effect on the ATP-sensitive K+ channel, and ADP was less effective than ATP. Thus, the ATP-sensitive K+ channel seems to be important for regulation of cellular energy metabolism in the control of membrane excitability.

ATP-regulated K + channels in cardiac muscle

A ROLE for abnormal lipid metabolism in the pathogenesis of atherosclerosis was suggested over a century ago, when Virchow proposed that transport of plasma lipids into the walls of blood vessels contributed to the development of atheromatous lesions. Lipid abnormalities are now firmly established as one factor leading to ischemic heart disease, although the mechanism by which they lead to coronary artery occlusion remains incompletely understood. More recently, abnormalities of lipid metabolism have been implicated in another quite different aspect of the pathogenesis of ischemic heart disease. A large body of evidence now indicates that altered lipid metabolism can alter cardiac function by changing the properties of cardiac cell membranes, and that these functional changes may contribute to the decline in myocardial contractility, the arrhythmias, and the eventual cell death that follow coronary artery occlusion. This article will review some of these disorders in lipid metabolism and possible mechanisms by which they might modify membrane function in the ischemic heart. Disorders of Lipid Metabolism in the Ischemic Heart There are now at least three well-defined mechanisms by which lipid metabolism may be altered in the heart after coronary artery occlusion (Table 1). Each of these mechanisms has been implicated in the pathogenesis of the cardiac abnormalities seen in patients who sustain an acute myocardial infarction.

BRIEF REVIEWS Lipid-Membrane Interactions and the Pathogenesis of Ischemic Damage in the Myocardium

Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium.

ATP is normally available in cells at millimolar concentrations and is "buffered" by intracellular pools of other high-energy phosphates, such as creatine phosphate. Thus intracellular [ATP] [( ATP...

Adenosine triphosphate-sensitive potassium channels in the cardiovascular system.

The evolution of premature ventricular contractions (PVCs) in acute myocardial infarction was studied by recording bipolar potentials from the left ventricle before and after coronary artery occlusion in dogs. The potentials were recorded from 154 locations in the left ventricular wall as well as at the endocardial and epicardial surfaces. Desynchronization and marked slowing of previously uniform activation was noted and resembled abbreviated, local fibrillation. The dissociation of excitation was either simple, characterized by fragmentation into single delayed spikes, or complex, characterized by numerous spikes. Sustained, desynchronized activity, confined to local myocardial areas, was observed up to 215 msec after the onset of activation. These local areas of sustained excitation functioned as a source of re-entrant activity and were associated with PVCs. Histochemical stains of myocardium indicated a relationship between the inhomogeneous distribution of ischemia (stain) and the desynchronization o...

Slow ventricular activation in acute myocardial infarction. A source of re-entrant premature ventricular contractions.

Im Sauerstoffmangel fallen nach einiger Zeit beim l~erv und Skeletmuskel das Ruhennd Aktionslootential ab, die Anstiegsdauer wird l~nger und die Leitungsgeschwindigkeit der Erregung nimmt ab (G~~Al~»S, SI~~~s~0, 31, CowA~3 TI~AIITw~rs et al. 84). Alle diese Ver~nderungen zeigt auch der Herzmnskel, doch ist für ihn charakteristisch die starke Verkürzung und Abflachung der Repolarisation, der Plate~uve rh l s t (Sc~IÜTZ 27, ~-~]~GGLI~ n. NO:B~]~ 11, E ~ K u. SC]3[fl_]~~JEI~6). Weiterhin unterscheidet sich der Herzmuskel noch vom Skeletmnskel durch seine wesentlich größere Empfindlichkeit gegen Sauerstoffmangel. Diese Ergebnisse wurden am Warmblüterherzen in sitn gewonnen, der Sauerstoffmangel durch Abstellen der Atempumpe oder durch Stickstoffbeatmung erreicht und der Al~ionsstrom nach dem Prinzip des ScHÜTZschen Herzwandknotens (in den Versuchen von EI~K u. SCI~AEI~EI¢ mit einer Mikrosogelektrode) monophasisch abgeleitet. Die genaueren Bedingungen sowohl in bezug auf den Grad des Sauerstoffmangels als auch die quantitative Erfassnng der PoLentialveränderun6en sind mit diesen ~e*hoden nicht unbedingt definiert, obwohl sie recht gut geeignet sind, den Plateauverlust zu messen. Unsere Arbeit will nun mit der l~ethode der in*racellulgren Ableitung in vitro bei genau bekannter Sanerstoffkonzentration die Entwicklung des Plateauverlustes untersuchen und diesen in Beziehung zu Änderungen der Potentialhöhen, der Anstiegsdauer und Leitnngsgeschwindigkeit setzen. Bisher wurde am Myokard des Warmblüters in vitro mit der Capillarelektrode hanptsgchlich am P~mKnVJE~&den (Dl%2*~I'El% u. W~II)lVI2klqlf 5, ~I~I%AUTWEIIf u. ZIIqK 33, TRAUTWErN el a1.85), dazu am Vorhof der Katze (BlraG~~ u. TEl~l~OVX 1, 2) und am Papillarmuskel der Katze (I-Iol~l~~I~lv u. SvoxLI~G 14) gearbeitet. Besonders bietet sich der Pul~KI~lJE-l~aden wegen seiner l~einheit, seiner geringen mechanischen Bewegungen, und seiner großen Resistenz gegenüber Sauerstoffmangel als geeignetes Prgparat an. Eine Untersuchung

U. Gottstein

Papers

Der Aktionsstrom der Myokardfaser im Sauerstoffmangel

The action current of the myocardial fibers in oxygen deficiency