The actions of ouabain on intercellular coupling and conduction velocity in mammalian ventricular muscle.

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Abstract
The effects of ouabain on the electrical coupling between cells and the conduction velocity, .theta., were studied in ventricular muscle preparations from calf and cow hearts using a silicon-oil-chamber. After 90 min of exposure to 2 .times. 10-6 M ouabain, an increase of the inside longitudinal resistance, Ri, from 420 .OMEGA. cm to 1032 .OMEGA. cm was observed. Assuming a constant myoplasmic resistivity this presumably reflects a reduced electrical coupling between myocardial cells. Concomitantly, .theta. was decreased from 50.3 to 29.4 cm/s. This change could be explained by the observed alterations in the maximal rate of rise of the action potential, (dV/dt)max, the amplitude of the action potential, Vp, the membrane capacity Cf, and the sum, respectively, of the inside and outside longitudinal resistance per unit distance (ri+ro). Quantitatively, about 60% of the decrease of .theta. could be accounted for by the experimentally determined increase of Ri. Time course studies revealed a biphasic action of ouabain on Ri. An early dose-dependent drop in Ri, equivalent to an improvement of the intercellular coupling, was followed by a delayed massive increase in Ri, whose onset and magnitude were also concentration-dependent. The delayed increase in Ri was associated with an increase of the diastolic tension. Toxic ouabain doses (2 .times. 10-6 M) produced irreversible changes on both parameters, but therapeutic doses (< 5 .times. 10-7 M) affected neither of them. Reversible effects on both parameters were observed at an intermediate drug concentration (10-6 M). The strong correlation between decoupling and contracture is consistent with the idea that the intracellular Ca concentration, [Ca]i, is involved in the control of the nexal conductance. This is supported by the finding that increasing the extracellular Ca concentration, [Ca]o, accelerated the ouabain-induced decoupling, whereas reducing [Ca]o retarded it. The contracture slightly preceded the increase in Ri. The threshold [Ca]i for the electrical decoupling between cells must be somewhat larger than the threshold level for the tension activation. The delayed increase in Ri is compatible with an inhibition of the Na pump which according to the Na-lag hypothesis predicts an increase of [Ca]i secondary to a Na-accumulation. The early drop in Ri can either be explained by a stimulation of the Na pump, or by a non-monotonic relationship between Ri and [Ca]i.