Biomedical subjects

M Reiter

Publications and source records attributed to M Reiter.

At least 109 records · Page 6Linked to original sources

PubMed1975

The relation between the effects of veratridine on action potential and contraction in mammalian ventricular myocardium.

In the isolated papillary muscle of the guinea pig veratridine produces an increase of the force of contraction by increasing the rate of force development. Time to peak force is slightly reduced, whereas relaxation time is markedly prolonged. Threshold, half-maximally and maximally effective concentrations for the positive inotropic effect are 0.1, 0.4 and 1.6 muM, respectively. 2. The positive inotropic effect of the maximally effective concentration of veratridine amounts to 68% of the maximum positive inotropic effect of dihydro-ouabain tested on the same muscle (N = 12). 3. Veratridine prolongs the action potential (AP) by delaying repolarization. The effect is concentration-dependent (range: 0.4--3.2 muM); it requires 1--2 hrs of maintained exposure to reach a steady state and is only slowly reversible upon removal of the drug. A concentration causing a nearly maximal positive inotropic effect (0.8 muM) does not affect resting potential or rate of rise of the AP; the overshoot is slightly depressed. 4. Tetrodotoxin (5--16 muM) reversibly inhibits both AP prolongation and positive inotropic effect of veratridine by shifting the concentration-effect curves for these effects to higher concentrations of veratridine. It also prevents veratridine-induced spontaneous activity. 5. Dihydro-ouabain or reduction of [K]o below 5.9 mM augument the positive inotropic effect of veratridine, while the interaction between veratridine and noradrenaline is additive. 6. The positive inotropic effect of 1.6 muM veratridine declines progressively when the contraction frequency is reduced below 0.5 Hz; rested-state contractions (at 0.004 Hz) are not increased by 1.6 muM veratridine. 7. It is concluded that (a) veratridine delays repolarization by prolonging the Na permeability component which is mediated by the fast Na channels; (b) this specific sarcolemmal effect of veratridine is the sole cause for its positive inotropic action by effecting an increase of [Na]i which probably leads to a subsequent increase of Ca uptake.

Action Potentials↗

PubMed1975

Adrenoceptors in cardiac ventricular muscle and changes in duration of action potential caused by noradrenaline and isoprenaline.

1. On guinea-pig papillary muscle we investigated whether a prolonging effect of noradrenaline on the duration of the cardiac ventricular action potential (AP) is attributable to an action on beta-adrenoceptors. 2. Propranolol (5 X 10(-6) M), which itself shortens AP (at 90% repolarization level), inhibits both effects of noradrenaline on the AP, i.e. the sustained prolongation by low concentrations (10(-7)--10(-6)M) and the steady-state shortening which follows an initial prolongation by a high concentration (10(-5)M). In the presence of propranolol, the prlonging effect of noradrenaline is shifted to higher concentrations (10(-6)--10(-5)M). This prolongation of AP duration does not exceed the prior shortening effect by propranolol; it is not prevented by 10(-5)M phentolamine. 3. Phentolamine, which itself prolongs AP duration, inhibits neither the initial prolongation nor the steady-state shortening of the AP by 10(-5)M noradrenaline. Instead, the biphasic change in AP duration as well as the positive inotropic effect of 10(-5)M noradrenaline are enhanced in the presence of 3Z10(-6)M phentolamine. 4. The effect of isoprenaline on the duration of AP qualitatively resembles that of noradrenaline. In a concentration of 10(-8)M, isoprenaline produces a sustained prolongation of the AP; concentrations of 10(-7)M and 10(-6)M cause an initial prolongation which is followed by a steady-state shortening. These effects are inhibited by propranolol. 5. It is concluded that not only the steady-state shortening effect on AP duration by 10(-5)M noradrenaline but also the prolongation of AP, induced by lower noradrenaline concentrations (10(-7)--10(-6)M), are mediated solely by an action on beta-adrenoceptors.

Action Potentials↗

PubMed1975

Frequency-force relationship in guinea-pig ventricular myocardium as influenced by magnesium.

1. In guinea-pig papillary muscle, the characteristic relation between force of contraction and frequency is changed by the sithdrawal of magnesium from the incubation medium. In magnesium-free solution, reduction of contraction frequency below 0.1 Hz leads to an increase in force of contraction which reaches its maximum at a frequency of 0.00166 Hz (i.e., one contraction every 10 min). After magnesium withdrawal, the frequency-force relationship in guinea-pig ventricular muscle resembles that of guinea-pig atrial muscle in magnesium-containing solution. 2. The increase by magnesium withdrawal in contractile force of guinea-pig papillary muscles contracting at low frequencies is the result of an increase in contraction velocity. The time to peak force is shortened and the relaxation time is prolonged. 3. After obtaining steady-state values of contractile force at 1 Hz contraction frequency, stimulation was terminated and the time course of changes in the inherent contractile activity of the muscle was determined by eliciting single contractions at time intervals of between 0.5 and 10 min duration. After cessation of stimulation, the contractile activity declines exponentially in solution containing 1.2 mM Mg2+; in magnesium-free solution an initial decline is followed by a slowly developing increase. This rise in contractile activity is reduced at 3.2 mM Ca2+ by the presence of 0.075 mM Mg2+ and is prevented by 0.3 mM Mg2+. 4. The increase in contractile activity obtained in the papillary muscle during rest by magnesium withdrawal depends in its magnitude on [Ca2+]0. 5. The rested-state contractile activity of ventricular muscle in magnesium-free solution is reduced by 75% with the first and by 90% with the second contraction after onset of 1 Hz stimulation. 6. Possible mechanisms are discussed by which Mg2+ inhibits the development of rested-state contractile activity in the guinea-pig ventricular myocardium.

Animals↗

PubMed1975

Cardiac action potential and inotropic effect of noradrenaline and calcium.

1. Noradrenaline biphasically affects the duration of the action potential (AP) of guinea-pig cardiac ventricular muscle. Low concentrations (10-7M) prolong the AP duration, while high (10-5M) 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. 2. 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 amximum always occur during the subsequent phase of AP-shortening. 3. In essential aspects the effect of noradrenaline on AP duration and contractile force resembles the effect of an increase in [Ca-2+]o:AP duration is changed biphasically by noradrenaline in the same way as by an increase in [Ca-2+]o: in both cases an increase in force of contraction is related only to the AP-shortening effect. - But, unlike noradrenaline, calcium at concentrations higher than 1.2mM 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. 4. The similarity of some of the effects of noradrenaline and calcium (i.e., prolongation of AP at low [Ca-2+]o: parallelism of positive inotropic effect and AP-shortening effect) indicated ahat 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 [Ca-2+]o), an additional influence on the membrane property must be assumed.

Action Potentials↗

PubMed1975