Long-term effect of ouabain and sodium pump inhibition on a neuronal membrane.

1. The long-term effects of ouabain on the membrane potential of the Anisodoris giant neurone (G cell) were examined in cells maintained for periods of up to 15 hr at 11-13 degrees C.2. In the presence of ouabain (5 x 10(-4)M), the membrane potential depolarized to a constant level for 1-4 hr, then hyperpolarized for 5-7 hr after which it gradually depolarized again.3. During the hyperpolarizing phase, after 6-8 hr in ouabain, [K](1) fell approximately 50%, [Na](1) increased 50-100% and the P(Na)/P(K) ratio decreased to 25% of its initial value.4. After 8 hr in ouabain the membrane conductance increased two- to fourfold. This increase was independent of temperature and membrane rectification.5. The K permeability (P(K)) was calculated from the constant field equation, and showed a fourfold increase after long-term treatment with ouabain. This rise in P(K) probably underlies the membrane hyperpolarization and the decrease in the P(Na)/P(K) ratio.6. It is suggested that inhibition of the Na(+) pump with ouabain causes a gradual rise in [Na](1) which secondarily leads to Ca(2+) uptake, an increase in [Ca](1), and thereby an increase in P(K).