Cardiac action potential and inotropic effect of noradrenaline and calcium

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Abstract
Noradrenaline biphasically affects the duration of the action potential (AP) of guinea-pig cardiac ventricular muscle. Low concentrations (10−7 M) prolong the AP duration, while high (10−5 M) concentrations shorten it after an initial prolongation. The extent of the AP-prolonging effect is more marked at low (0.3 and 0.6 mM) than at high (2.4 or 4.8 mM) extracellular calcium concentrations. When the concentration of noradrenaline is cumulatively increased, the AP duration is always transiently prolonged, even if the AP is shortened in the second phase of the preceding noradrenaline effect. The AP-prolonging effect begins immediately after the addition of noradrenaline. The positive inotropic effect does not appear until the maximum of the AP-prolonging phase has been reached. Its continued rise and maximum always occur during the subsequent phase of AP-shortening. In essential aspects the effect of noradrenaline on AP duration and contractile force resembles the effect of an increase in [Ca2+]o: AP duration is changed biphasically by noradrenaline in the same way as by an increase in [Ca2+]o; in both cases an increase in force of contraction is releated only to the AP-shortening effect. —But, unlike noradrenaline, calcium at concentrations higher than 1.2 mM produces no transitory initial prolongation of AP duration. And, whereas higher concentrations of calcium shorten the plateau-phase of the AP in particular, noradrenaline has the most pronounced shortening effect on the late rapid repolarisation-phase of the AP. The similarity of some of the effects of noradrenaline and calcium (i.e., prolongation of AP at low [Ca2+]o; parallelism of positive inotropic effect and AP-shortening effect) indicates that at least part of the noradrenaline effect on the AP is the expression of an enhancement of calcium influx. For the effect of noradrenaline which is unlike that of calcium (i.e., prolongation of the relative plateau duration and transient prolongation of AP duration at high [Ca2+]o, an additional influence on the membrane property must be assumed.

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