Transient outward current and rate dependence of action potential duration in rabbit cardiac ventricular muscle

Abstract

A conventional (single sucrose gap) voltage clamp technique was employed to investigate the rate dependence of ionic currents activated in the plateau range of potential in the rabbit ventricular muscle. A transient outward current of increasing amplitude was observed when the period of rest preceding the test voltage clamp pulse was increased from 0.7-60 s. The action potential duration was short when the transient outward current peak (100-150 ms after the voltage clamp pulse beginning) was high under the studied conditions of stimulation (interbeat intervals 0.7-60 s). The rate dependent transient outward current was small at low levels of depolarization above the resting potential (40 mV), had a maximum at some 90-100 mV and decreased at more positive potentials. This current was sensitive to the simultaneous application of 4-aminopyridine and calcium substitution with strontium in the Tyrode solution. It is suggested that the transient outward current is probably responsible for the changes of the action potential duration in rabbit papillary muscles when the interbeat interval varies from some 0.7-60 s.

Rate-dependency of Action Potential Duration and Refractoriness in Isolated Myocytes from the Rabbit AV Node and Atrium

“…14,19 Slow reactivation of I TO is species-dependent and accounts for the APD-shortening at slow rates which occurs in those tissues of certain species (rabbit and rat) in which I TO is a major repolarising current. 14,20 Since I TO both activates and inactivates rapidly in the potential range of phase 1, it might not be expected to contribute to later phases of repolarisation.…”

“…15 However, APDshortening resulting from low rates of stimulation, as demonstrated in hearts of both the rabbit 16 and rat, 17 has been correlated with a slow reactivation of I TO1 , the 4-aminopyridine (4-AP)-sensitive component of the transient outward K + current, I TO . 14,18,19 The reactivation kinetics of I TO is species-dependent, 20 which may explain the lack of APD-shortening at low rates in human, 12 in contrast to rabbit myocardium. Moreover, in the rabbit, the contribution of I TO to the APD rate-relation in the AV node might be expected to be less than in the atrium, due to the relatively small I TO in mid-nodal cells.…”

Preceding Stimulus Frequency-Dependent Potentiation of the Postrest Shortening of the Action Potential Duration in Rabbits.

“…4) We also reported that the postrest shortening was inhibited to a certain extent by the application of 4-AP at concentrations up to 10 mM. However, additional application of ryanodine was necessary to completely abolish the postrest shortening.…”

“…Mechanisms: Since a long diastolic interval allows recovery from inactivation in the 4-AP sensitive Ito, the current has been attributed to the postrest shortening in the rabbit ventricular myocardium. [3][4][5] However, blockade of 4-AP sensitive Ito is not sufficient to completely abolish the postrest shortening.…”

“…3) These observations indicate involvement of the sarcoplasmic reticulum (SR), in addition to the slower recovery from inactivation in the 4-AP sensitive transient outward current (Ito), 4,5) in the regulation of the APD after a prolonged pause. We therefore hypothesized that an increase in conditioning stimulus frequency preceding the rest period enhances utilization of activator calcium (Ca 2+ ) released from the SR, resulting in potentiation of the postrest shortening.…”