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University Laboratory of Physiology, University of Oxford.

1. A rapid solution-changing system using a solenoid was set up. The half-time for changing the external solution surrounding a ventricular cardiac cell was 7.2 +/- 1.4 ms, whereas the time needed to change 90% of this solution was 48.5 +/- 7.9 ms. This rapid switching system was used to reduce the external sodium concentration at different moments during the action potential (recorded using the whole-cell method) to 50% of its original value. This was performed in order to investigate the effect on the shape and duration of the action potential of modifying the activity of the sodium-calcium exchanger. 2. A diminution of the action potential duration was seen irrespective of the substitute used for reducing the NaCl concentration from 140 to 70 mM. The magnitude of this diminution depended on the presence or absence of EGTA (5 mM) in the pipette solution and also on the moment during the action potential at which the NaCl substitution occurred. 3. Some differences were observed depending on whether the NaCl substitute used was lithium chloride or choline chloride. When choline chloride or N-methyl-D-glucamine was used as the NaCl substitute, the amplitude of the action potential was slightly reduced (by 2-5 mV) when the solution was changed 40 ms before the action potential was triggered. This reduction was never observed when LiCl was used as the NaCl substitute. 4. The effects on the shape of the action potential of changing from a solution containing 140 mM NaCl to one containing 70 mM NaCl and 70 mM LiCl were much more rapid when these changes occurred at a later stage during the action potential. The rate of repolarization was more than doubled when the change occurred at a late stage of the action potential but was hardly changed at the beginning of the plateau. 5. These experiments confirm the role of the sodium-calcium exchange current in determining the duration of the mammalian ventricular action potential. However, it is also possible that the sodium background current plays a significant role in determining the shape of the action potential.

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