Voltage-dependent potentiation of the slow inward current in frog atrium.

1. Slow inward currents, isi, were measured using a double sucrose-gap voltage-clamp technique during experiments involving different depolarization protocols. 2. Following short rest periods, repetitive stimulation gave rise to slow inward currents which changed progressively in a voltage-dependent manner. Small voltage depolarizations gave rise to initial small decreases in current (negative 'staircase'). The current usually then showed a secondary increase but still remained, in most cases, below the control amplitude. Larger depolarizations produced increasingly larger and more rapidly rising positive current 'staircases'. 3. The amount of increase in current magnitude during repetitive depolarization was more strongly dependent on the size of the voltage step than on the amplitude of the initial current. 4. Twin-pulse experiments having a fixed interval between pulses (usually 1.0 sec), showed that 'test' pulses produced more slow inward current than preceding 'conditioning' depolarizations. The augmentation was larger following conditioning pulses of longer duration. Current augmentation was larger during 'staircase' obtained with longer pulses. 5. Following constant duration 'conditioning' depolarizations, varying the interpulse interval showed that the slow inward current flowing during the 'test' pulse could be augmented following intervals of as long as 6-8 sec. 6. Small pre-pulses also augmented the slow inward currents obtained in response to 'tet' pulses. 7. Experiments in calcium-free solutions (with EGTA) showed qualitatively similar 'staircase' effects and current augmentation following preceding depolarizations. 8. Experiments in which sodium was replaced by lithium gave rise to larger slow inward currents. The 'staircase' for such currents developed in a similar manner to that seen under control conditions. 9. It is concluded that slow inward current augmentation is produced by membrane depolarization in a fashion which is at least partially independent of calcium or sodium ion influx.