Effect of repetitive activity upon intracellular pH, sodium and contraction in sheep cardiac Purkinje fibres.

The influence of repetitive activity upon intracellular pH (pHi), intracellular Na+ activity (aNA(i)) and contraction was examined in isolated sheep cardiac Purkinje fibres. Ion‐selective microelectrodes were used to measure intracellular Na+ and H+ ion activity. Twitch tension was elicited by field stimulation or by depolarizing pulses applied using a two‐microelectrode voltage clamp. Experiments were performed in HEPES‐buffered solution equilibrated either with air or 100% O2. 2. An increase in action potential frequency from a basal rate of 0.1 to 1‐4 Hz induced a reversible fall in pHi and a reversible rise in aNa(i). These effects reached a steady state 3‐10 min following an increase in stimulation frequency, and showed a linear dependence on frequency with a mean slope of 0.023 pH units Hz‐1 and 0.57 mmol l‐1 Hz‐1, respectively. The rise in total intracellular acid and aNa(i) associated with a single action potential was estimated as 5.3 mu equiv l‐1 of acid and 3.5 mu equiv l‐1 of Na+. 3. At action potential frequencies greater than 1 Hz, the rate‐dependent rise in aNa(i) was usually accompanied by a positive force staircase. 4. The fall in pHi following a rate increase also occurred when fibres were bathed in Tyrode solution equilibrated with 23 mM‐HCO3‐ plus nominally 5% CO2/95% O2. In these cases, however, the fall in pHi was halved in magnitude. 5. In fibres exposed to strophanthidin (0.5 microM), the rate‐dependent fall in pHi was doubled in magnitude and its time course was more variable than under drug‐free conditions. The rate‐dependent rise in aiNa was also usually larger in strophanthidin. 6. In order to examine the influence of the rate‐dependent acidosis on developed tension, the acidosis was reversed experimentally by adding 2 mmol l‐1 NH4Cl to the bathing solution. This produced a rise in pHi accompanied by a large increase in twitch tension. Such an effect of pHi upon tension was quantitatively similar to that observed in previous work on Purkinje fibres (Vaughan‐Jones, Eisner & Lederer, 1987). 7. It is concluded that the rate dependence of pHi will influence both the magnitude and the time course of an inotropic response to a change in heart rate.