Effect of rate‐dependent changes in the transient outward current on the action potential in sheep Purkinje fibres.

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Abstract
The rate of membrane potential change during the initial phase of rapid repolarization of the action potential in sheep Purkinje fibers was measured by electronic differentiation. Phase-plane analysis revealed that the potential dependence of rapid repolarization corresponds to the potential range over which the transient outward current, Ito, is recorded in voltage clamp experiments. The initial rate of repolarization is strongly rate-dependent and it is markedly reduced at high rates. The effect of high rates of stimulation on the phase-plane diagram is consistent with a reduction in Ito. After an increase or decrease in rate, there is an abrupt change in the initial rate of repolarization in the 1st response followed by slower changes over several hundred responses. Recovery of the initial rate of repolarization occurs in 2 distinct phases after repetitive activity; there is a rapid, approximately exponential phase of recovery in the first 10 s which is followed by a slower phase of recovery lasting several hundred seconds. The rate-dependent changes in the initial rate of repolarization are abolished by 4-aminopyridine, 0.5-1.0 mmol/l. The rate-dependent changes in the initial phase of repolarization are due to the similar changes in Ito. Rate-dependent changes in peak tension were measured and they bear no relationship to the changes in the initial rate of repolarization. The major component of the transient outward current in sheep Purkinje fibers is unlikely to be a Ca-activated current.