Ouabain effects on intracellular potassium activity and contractile force in cat papillary muscle.

Abstract

A B S T R A C T The relationship between the positive inotropic and toxic effects of cardiac glycosides and their effects on intracellular ionic composition is incompletely defined. We measured intracellular potassium activity (ak), extracellular potassium activity (at), resting potential, action potential duration, and contractile force at 32°C in paired papillary muscles from feline right ventricles exposed to ouabain. Muscles used for electrophysiological measurements were quiescent except for isolated stimulation to confirm impalement and record action potential duration. Muscles used for contractile force measurements were quiescent except for 4-min periods when force was measured at a cycle length of 1,400 ms. Muscle length was adjusted to achieve 50% of maximal tension at this cycle length before each experiment. In four experiments, ai and contractile force were measured in the same muscle. a' was measured with single and double-barrel K-sensitive electrodes. At 10 nM ouabain, action potential duration is prolonged. Among the concentrations tested, the threshold for a clear positive inotropic effect is 0.1 ,uM ouabain. The threshold for decrease in ak, increase in aeK, and decrease in membrane potential is 1 ,uM, at which concentration toxic signs develop, including arrhythmias, aftercontractions, and alteration in the staircase response of contractile force to repetitive stimulation. Ouabain need not change a' to effect positive inotropy in ventricular muscle, a relationship different from that reported between [K], (intracellular potassium concentration) and positive inotropy. Higher ouabain concentrations, which others have shown to clearly inhibit active Na and K transport, are shown to upset

Regional changes in intracellular potassium and sodium activity after healing of experimental myocardial infarction in cats.

“…The results of the present study demonstrated that ale was indeed different in the infarct and border zone cells. The value of a' in ventricular muscle cells from normal zones was similar to that previously reported for normal cat papillary muscle cells (Browning et al, 1981). In addition, al< in infarct zone cells was similar to that in normal zone cells.…”

“…In an initial series of three experiments, preparations were exposed to 10~6 ouabain for 60 minutes, using the method of Browning et al (1981). However, all preparations became inexitable within 60 minutes exposure to 10~6 M ouabain, making it difficult to measure ak-In a second series of nine experiments, we lowered the ouabain concentration to 5 X 10" 7 M, and the measurements were made 60 minutes after superfusion with the drug.…”

Electrophysiological studies of some semisynthetic cardiac glycoside derivatives in isolated papillary muscle of the guinea‐pig

“…The time-independent potassium conductance also increases and serves as a plausible explanation for the decrease in action potential amplitude (Greenspan & Morad, 1975). Membrane depolarization is observed only with higher concentrations which cause effective pump inhibition and therefore result in substantial intracellular potassium loss (Muller, 1965;Bentfeld, Luillmann, Peters & Proppe, 1977;Browning, Guarnieri & Strauss, 1981). Also, during effective pump inhibition the electrogenic contribution to the membrane potential is diminished (Daut & Rudel, 1982) which causes further depolarization.…”

Internal Potassium Activity in Ferret Ventricular Muscle

“…Out of nine experiments (sixteen impalements), four experiments (five impalements) met all of these criteria and they are tabulated in Table 1 Because of diffusion of K+ out of the tip of a 3 mol KCI/I electrode it is not possible to use it to fill the reference barrel ofdouble-barrelled electrodes (see Stoner, Natke & Dixon, 1984). In these experiments it was found that neither 1 or 3 mol Li acetate/l or indeed 3 mol Browning, Guarnieri & Strauss (1981) Guinea-pig 37 137…”