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Changes in the intracellular sodium activity of sheep heart Purkinje fibres produced by calcium and other divalent cations.

1. The intracellular Na activity of sheep heart Purkinje fibres was recorded with Na+‐sensitive glass micro‐electrodes. The effects of various external divalent cations on the intracellular Na activity were investigated. 2. Raising the external concentration of divalent cations (Ca, Mg, Mn, Sr or Ba) from 3 to 16 mM resulted in a decrease in the intracellular Na activity of 10‐50%. 3. Raising the external concentration of Ca, Sr or Ba could produce a decrease in the intracellular Na activity even when the Na‐K pump was inhibited (with strophanthidin, 10(‐5) M); but raising the external concentration of Mg or Mn could not. 4. Mn inhibited the decrease in the intracellular Na activity produced by raising external Ca while the Na‐K pump was inhibited. 5. Raising external Ca or adding Mn reduced the rate of rise of the intracellular Na activity on inhibition of the Na‐K pump. 6. The removal of external K resulted in an increase in the intracellular Na activity. This increase could be stopped and even reversed by raising external Ca. 7. Removal of divalent cations from the external solution produced an increase in the intracellular Na activity. However, replacing external Ca and Mg by another divalent cation, e.g. Mn, did not result in a rise in the intracellular Na activity, except when the Na‐K pump was inhibited. 8. The intracellular Na activity decreased by approximately 50% for a tenfold increase in the external Ca concentration. 9. The extent of the decrease in internal Na activity produced by raising external Ca was directly proportional to the internal Na activity before external Ca was raised. 10. We conclude that external Ca influences the intracellular Na activity in two ways: (a) by changing the passive Na influx: the resultant change in the intracellular Na depends on the activity of the Na‐K pump; and (b) by a process where internal Na ions are exchanged for external Ca ions.