부산대학교 도서관

1. Whole‐cell recording from isolated rat and guinea‐pig ventricular myocytes revealed a change of the cardiac Na+ pump current (Ip)‐voltage (V) relationship by cardiac glycosides, specific inhibitors of the Na(+)‐K+ pump. 2. Dihydro‐ouabain (DHO) diminished Ip in rat ventricular cells at 0 mV in a concentration‐dependent manner. 3. The concentration‐response curve of Ip inhibition caused by DHO was shifted to higher [DHO] at higher extracellular K+ concentrations ([K+]o) or at more negative membrane potentials. 4. In rat myocytes, DHO immediately flattened the normalized cardiac Ip‐V curve and evoked or enhanced a region of negative slope. 5. Ouabain, at concentrations which caused a comparable inhibition of Ip, exerted DHO‐like effects on the Ip‐V relationship of rat ventricular myocytes. However, the effects developed more slowly. 6. A slowly developing alteration of the Ip‐V curve was also observed upon application of DHO to guinea‐pig ventricular cells. The range of [DHO] used was about 100‐fold lower than that applied to rat ventricular cells, but was equally effective for Ip inhibition. 7. Increasing the K+ concentration of DHO‐containing media affected the existing equilibrium of DHO binding to the cardiac Na(+)‐K+ pump. A new equilibrium was reached within about 3 s in rat ventricular myocytes, but only within about 50 s in guinea‐pig ventricular cells under the experimental conditions chosen. 8. It is concluded that the changes of the cardiac Ip‐V curve induced by cardiac glycosides are mediated by voltage‐dependent variations of the local [K+]o at the K+ binding sites of the Na(+)‐K+ pump in an ‘access channel’. The variations were estimated by means of the Boltzmann equation. The estimations agreed with those derived from the measured DHO binding to the Na(+)‐K+ pump at various [K+]o. A new equilibrium of glycoside binding to the pump is established at the altered [K+]o. The time necessary to reach the new binding equilibrium varies with the cardioactive steroid, its concentration and the glycoside sensitivity of the cardiac cells.