A study of the effect of the rate of stimulation on the transient outward current in sheep cardiac Purkinje fibres.

1. The transient outward current, Ito, of sheep Purkinje fibres has been recorded using the two micro-electrode voltage clamp technique. 2. Ito is strongly rate-dependent: the magnitude of Ito activated during a test voltage clamp pulse after a train of action potentials is less at higher rates of stimulation. 3. After an increase or decrease in rate there is an abrupt change in Ito in the first response followed by slower changes over the next several hundred responses. 4. When a preparation is rested after repetitive activity Ito recovers in two phages: there is an initial rapid, approximately exponential phase of recovery in the first 10 s which is probably due to reactivation; this is followed by a slower phase of recovery lasting several hundred seconds. 5. Curves showing the time course of reactivation of Ito have been obtained at different rates. At high rates the curves approach smaller values of Ito and the steady-state control values of the current occur on the shoulder of the curves, i.e. before reactivation is complete. 6. It is proposed that the reduction of Ito at high rates is due to two factors: incomplete reactivation which accounts for the rapid changes of Ito and a second unknown factor which accounts for the slower changes in the current. 7. Inspection of current-voltage relationship for Ito suggests that the reduction of Ito at high rates is mainly due to a decrease of conductance rather than to a reduction of the reversal potential. 8. Replacement of the calcium in the bathing solution by strontium does not abolish Ito in sheep Purkinje fibres, suggesting that the current is distinct from the transient outward current in calf Purkinje fibres described by Siegelbaum & Tsien (1980).