Effects of repetitive activity on developed force and intracellular sodium in isolated sheep and dog Purkinje fibres.

1. When cardiac muscle is stimulated after a rest there is a gradual increase in force development over several minutes. The origin of this 'force staircase' was investigated in experiments on sheep and dog Purkinje fibres. Particular attention was paid to the possible role of changes in the intracellular Na+ activity (aNAi). 2. The first line of evidence for a role for aiNa came from a comparison of sheep and dog Purkinje fibres generating action potentials: after a change in the stimulus rate the slow changes of both aNai and force were monophasic in sheep but biphasic in dog preparations. 3. In the remaining experiments changes in aNai and force in sheep preparations were measured during 4 min trains of voltage-clamp pulses at a frequency of 2.5 Hz. 4. A number of these voltage-clamp experiments also indicated that changes in aNai are involved. Depending on the preparation and the duration of the pulses aNai rose or fell during a train-a rise in aNai was always associated with a gradual rise in force, whereas a fall in aNai was usually accompanied by a gradual fall in force. The addition of tetrodotoxin (TTX) or the use of a low holding potential reduced the progressive rises of both aNai and force, whereas the inclusion of a 10 mV hyperpolarization between pulses potentiated the progressive rises of both. 5. The effect of TTX on the staircase was more marked the longer the pulses during the train; this possibly indicates that the effect of aNai on the force staircase is complex and is more marked with longer pulses. 6. A rise in aNai was shown not to be the only factor underlying the progressive increase in force, because in many preparations a gradual rise in force occurred in spite of no change or even a fall of aNai. 7. It is concluded that an increase in aNai is involved in the slow increase in force during the staircase accompanying a train of action potentials, and that other factors are also involved; various possibilities are discussed.