Mechanisms Underlying the Shortening of the Action Potential at High and Low Stimulus Rates in Sheep Purkinje Fibres

The shortening of the action potential of sheep Purkinje fibres at high and low rates of stimulation has been investigated. The shortening of the action potential at high rates can be entirely accounted for by incomplete recovery of the plateau conductances between beats. When sufficient time is allowed for membrane recovery, a prolongation of the action potential, rather than a shortening, occurs at high frequencies. The effect on electrical activity of increasing the stimulus frequency is similar to decreasing the bathing K concentration. The possibility of a reduction in the cleft K concentration at high frequencies is discussed. The shortening of the action potential at low rates is unaffected by 4-amino pyridine (a blocker of the transient outward current, i_to) is abolished by D600 (a blocker of the second inward current, i_si) and by a rise in the bathing Ca concentration. It is concluded that i_si rather than i_to is involved in action potential shortening at low rates. Action potential shortening at low rates is closely associated with declines in the maximum diastolic potential and the pacemaker potential; all of these changes are abolished by ouabain (a blocker of the Na-K pump). It is concluded that the shortening of the action potential at low rates may be the result of a decline in i_si, which in turn is dependent on a decline in [Na]_i. It is suggested that the rate-dependent changes in the maximum diastolic potential, pacemaker potential and tension are also related to [Na]_i. As a summary the hypothesis in scheme 1 is put forward to account for the slow changes in action potential duration (a.p.d.), maximum diastolic potential (m.d.p.), pacemaker potential amplitude (p.p.) and tension at low heart rates. In this scheme all of the slow changes in electrical and mechanical activity ultimately depend on the changes in [Na]_i; this explains why the slow rate-dependent changes in action potential duration, maximum diastolic potential, pacemaker potential amplitude and tension occur with similar time courses. Notice that the decrease in Na-K pump current at low rates (which is known to occur) will also tend to lengthen the action potential and perhaps increase the pacemaker action potential amplitude, but these effects must be masked by the other processes. The possibility of an increase in the cleft K concentration at low rates is the most tentative step in this scheme but note that any factor that is linked to [Na]_i and which increases the K conductance (as does an increase in the K concentration) could also account for the changes in the pacemaker potential (but not the changes in the maximum diastolic potential).