Epicardial cells are more susceptible to the electrophysiological effects of ischemia than are endocardial cells. To explore the ionic basis for the differential electrophysiological responses to ischemia at the two sites, we used patch-clamp techniques to study the effects of ATP depletion on action potential duration and the ability of ATP-regulated K+ channels in single cells isolated from feline left ventricular endocardial and epicardial surfaces. During ATP depletion by treatment with 1 mM cyanide (CN-), shortening of action potential durations was significantly greater in epicardial cells than in endocardial cells. Thirty minutes after initiating exposure to 1 mM CN-, action potential duration at 90% repolarization was reduced to 0.70 +/- 0.12 of the control value for endocardial cells versus 0.39 +/- 0.18 for epicardial cells (p less than 0.01), and action potential duration at 20% repolarization was reduced to 0.72 +/- 0.13 for endocardial cells versus 0.12 +/- 0.09 for epicardial cells (p less than 0.01). In both endocardial and epicardial cells, the shortening of action potential by CN- treatment was partially reversed by 0.3 microM glibenclamide; the magnitude of reversal, however, was much greater in epicardial cells. After exposure to 1 mM CN-, the activity of ATP-regulated K+ channels in cell-attached membrane patches was significantly greater in epicardial cells than in endocardial cells. To study the dose-response relation between ATP concentration and open-state probability of the channels, intracellular surfaces of inside-out membrane patches containing ATP-regulated K+ channels were exposed to various concentrations of ATP (10-1,000 microM). The concentration of ATP that produced half-maximal inhibition of the channel was 23.6 +/- 21.9 microM in endocardial cells and 97.6 +/- 48.1 microM in epicardial cells (p less than 0.01). These data indicate that ATP-regulated K+ channels are activated by a smaller reduction in intracellular ATP in epicardial cells than in endocardial cells. The differential ATP sensitivity of ATP-regulated K+ channels in endocardial and epicardial cells may be responsible for the differential shortening in action potentials during ischemia at the two sites.

The mitral complex is a functional entity composed of the annulus, valve leaflets, chordae, and papillary muscles. The mechanical properties of the complex are dependent on the unique structural relations of the collagen in the leaflets and chordae. In the chordae the collagen is arranged in avascular columns. These columns interdigitate between muscle fibers in the papillary muscles, and the collagen is anchored to the myofiber membrane by microfibrils. In the leaflet the chordae are continuous with the dense fibrous tissue, forming a sheet of collagen which merges with the annulus. Within the leaflet there are cardiac muscle fibers in direct continuity with left atrial muscle. Contraction of isolated valve preparations can be initiated by electrical stimulation and is preceded by a propagated depolarization. Action potentials from cells in the middle third of the leaflet have a slow upstroke velocity, prominent plateau, and a characteristic positive afterpotential. Valve muscle electromechanical properties are markedly altered by 1 X 10~7M acetylcholine; this concentration has little effect on working left atrial muscle. In preparations containing portions of the left atrium and valve leaflet, the excitation wave spreads into the leaflet after electrical stimulation of the atrial muscle. This suggests that the accompanying contractile event may occur in situ before the initiation of systole.KEY WORDS acetylcholine mitral valve leaflet action potential comparative pathology papillary muscle length-force relation electrophysiology chordae tendineae left atrial muscle mitral excitation• The anatomical structures regulating the flow of blood at the mitral orifice have been termed the mitral complex (1). This is composed of the mitral annulus, valve leaflets, chordae tendineae, and papillary muscles. Mitral valvular fibrosis in man and dog is well known clinically and pathologically. In the dog, the abnormal physiological function resulting in mitral insufficiency may be related to structural alterations in one or more regions

The effects of diphenylbydantoin (DPH) were studied on isolated, perfused Purkinje fibers over a range of concentrations from lCh 8 to 10 -4 M. The time course of repolarization of the transmembrane action potential shortened due to abbreviation of all phases of repolarization. The effective refractory period also shortened during exposure to DPH, but to a lesser extent than the action potential. As a result the earliest effective test stimulus elicited action potentials with greater amplitude and dv/dt of phase 0 than under control conditions. In driven fibers with normal action potentials, DPH had little effect on the amplitude or rate of rise (dv/dt) of phase 0 of the action potential. In driven fibers which were partially depolarized, or those with low dv/dt of phase 0 despite normal resting potentials, DPH caused an increase in the rate of rise of phase 0 of the action potential. DPH caused a decrease in the firing rate of normal automatic fibers by decreasing the slope of phase 4 depolarization. In automatic fibers which showed generalized diastolic depolarization and decreased maximum diastolic potential, DPH caused an increase in the latter as well as a decrease in the slope of phase 4 depolarization.