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Biomedical subjects

G Droogmans

Publications and source records attributed to G Droogmans.

At least 163 records · Page 9Linked to original sources
PubMed1985

Na+-K+ ATPase, Na-Ca exchange, and excitation-contraction coupling in smooth muscle.

The evidence in favor of a direct role of active Na transport in the regulation of excitation-contraction coupling in vascular smooth muscle has been examined. The observations in vivo and those obtained in isolated tissues do not always lead to the same conclusions. The changes of the membrane potential obtained in vitro by slight reductions in, or increases of [K]o do not modify the resting potential of the cells sufficiently to make them contract. Applying K-free or Na-free medium on isolated tissues is a much more vigorous procedure than the limited changes of [K]o that can occur in vascular beds in situ. The Na-Ca exchange-mechanism does not seem to play a major role in those smooth-muscle cells that have been analyzed in detail, but even here the experimental procedures have neither given precise information about the composition of the intracellular compartment nor allowed sufficient control of the parameters studied. The comparison of membrane vesicles from smooth muscle and from cardiac muscle indicates that important differences exist in Na-Ca exchange and in activities of Na+-K+ ATPase and Ca2+-Mg2+ ATPase. These findings suggest a poor development of Na-Ca exchange in smooth muscle as compared to cardiac muscle. Finally, the changes in the Na metabolism of erythrocytes from hypertensives are mentioned, and the present difficulties of linking those changes to an increased reactivity of vascular smooth-muscle cells are briefly discussed.

Animals↗
PubMed1984

Cell membrane responsiveness and excitation-contraction coupling in smooth muscle.

In this study of the excitation-contraction coupling in arterial smooth-muscle cells, the relations between changes of the membrane potential, force development, and 45Ca exchange have been investigated. It is proposed that the cell membrane plays a primary role by regulating the Ca entry into smooth-muscle cells and by extruding the excess cytoplasmic Ca. The possible relation between the receptor-operated channels and the sarcoplasmic reticulum has been discussed, and the peculiar differences between exogenous noradrenaline and noradrenaline released from the nerve terminals have been described.

Animals↗
PubMed1984

Effects of 2-nicotinamidoethyl nitrate (Nicorandil) on excitation-contraction coupling in the smooth muscle cells of rabbit ear artery.

The effect of SG-75 (Nicorandil) on the neuromuscular transmission and smooth muscle membrane of the rabbit ear artery was investigated by means of intracellular microelectrodes, isometric tension recording and flux experiments. This agent caused a pronounced hyperpolarization of the cell membrane and a significant increase of the K-permeability. During perivascular nerve stimulation, the amplitude and the time constant of the falling phase of the excitatory junction potentials were reduced, causing a suppression of spike generation and of the concomitant contractile responses, but the release of [3H]noradrenaline was not affected. At high doses this agent inhibited significantly submaximal contractile responses induced by various stimuli. However, these effects could not be correlated with changes in 45Ca fluxes. It is suggested that although the effect of SG-75 could be due mainly to an increase of the K-permeability and the concomitant hyperpolarization, it might also reduce the force development by a mechanism which does not depend on a reduction of the concentration of ionized Ca in the cytoplasm.

Animals↗
PubMed1982

Membrane potential and excitation-contraction coupling in smooth muscle.

To describe the role of the membrane potential in the regulation of the excitation-contraction coupling of smooth muscle, two types of smooth muscle tissues, the tenia coli of the guinea pig and the ear artery of the rabbit, have been compared. The first tissue provides an example of electromechanical coupling, and the second one is characterized by pharmacomechanical coupling. Under physiologic conditions tenia coli present action potentials accompanied by an entry of Ca2+ into the cells. However, the calculated amount of Ca entering during an action potential is, according to several authors, insufficient to cause contraction. An alternative mechanism to increase the intracellular Ca2+ could be a Ca-induced or depolarization-induced Ca release. Application of acetylcholine increases the ion permeability of the plasma membrane, thereby causing an increase of the spike frequency and a membrane depolarization. In addition, it induces a release of cellular Ca. However, the changes of the membrane potential seem to be the primary regulatory factor in determining the activity of this tissue. In the ear artery the role of the membrane potential seems to be much less important than in tenia coli. There is no electrical activity, and norepinephrine induces a force development without depolarizing the cells. This agonist causes a release of Ca from an intracellular store and at the same time increases the Ca permeability of the membrane. We have obtained experimental evidence suggesting that norepinephrine could act primarily on a cellular Ca store close to the cell membrane. A depletion of this store could result in a rapid flow of external Ca into this store and from there into the cytoplasm. The receptor-operated channels would be incorporated in the plasma membrane-sarcoplasmic reticulum junction.

Acetylcholine↗
PubMed1981

Temperature-dependence of 45Ca fluxes and contraction in vascular smooth muscle cells of rabbit ear artery.

The effect of cooling from 35 to 20 degrees C on the 45Ca-exchange and on the contractile response of rabbit ear artery has been investigated. The amplitude of the contraction induced by K-depolarization at 20 degrees C is reduced to about 60% of its value at 35 degrees C, whereas the response to noradrenaline is not significantly affected. Cooling induces a 2 to 4-fold reduction of the 45Ca-efflux rate. This effect also occurs in Ca-free medium and in solutions containing 1 mM La. It also occurs in Na-free medium and in tissues in which the transmembrane Na-gradient has been reduced. At 20 degrees C, the 45Ca-influx in unstimulated tissues and in K-depolarized preparations is significantly lower than at 35 degrees C. In Ca-depleted tissues, i.e. tissues in which the noradrenaline-sensitive Ca-store has been emptied by a stimulation with the agonist in Ca-free solution, the 45Ca-influx is not significantly affected by cooling. The gradual depletion of the noradrenaline-sensitive Ca-store in Ca-free solutions is at 20 degrees C much slower than at 35 degrees C. The amount of Ca released by noradrenaline is not affected by cooling, whereas for the same amount of Ca released the contractile response is higher at 20 degrees C. These findings indicate that temperature affects the transmembrane Ca-extrusion and the Ca-influx through voltage-dependent channels. The properties of the noradrenaline-sensitive Ca-store are less sensitive to temperature.

Animals↗
PubMed1981

Exchange characteristics of the noradrenaline-sensitive calcium store in vascular smooth muscle cells or rabbit ear artery.

1. The amplitude of the noradrenaline-sensitive Ca stores has been estimated by measuring the amplitude of the transient contraction induced by the agonist in Ca-free solution. or by measuring the amount of 45Ca released under these conditions. 2. The rate of filling of this store after depletion is much faster than the rate of depletion in Ca-free solution, and depends on [Ca]o in the bathing solution. The degree of filling also depends on [Ca]o. 3. At the same [Ca]o the degree of filling is higher in K-depolarized tissues than in control tissues. However at 10 mM-[Ca]o and 5.9 mM-K the amount of Ca taken up by the store is larger than that after loading in 0.2 mM-Ca and 141.4 mM-K, although the tissues remain relaxed during loading at 5.9 mM-K and contracted at 141.4 mM-K. 4. The Ca antagonists D600 and nicardipine selectively block the contraction induced by K depolarization, but do not affect appreciably the noradrenaline-induced contraction. 5. The filling of the store is not significantly reduced by the presence of the Ca antagonists in solutions containing 5.9 mM-K. However these antagonists reduce the degree of filling in K-rich loading solution to a level which is lower than that observed in the control. 6. Mn blocks both the contraction induced by K-rich solution and the tonic component of the noradrenaline-induced contraction and its also inhibits filling of the store. 7. The results suggest that the filling of the store under physiological conditions occurs by a direct pathway between the store and the extracellular medium.

Animals↗
PubMed1979

Sodium and calcium interactions in vascular smooth muscle cells of the rabbit ear artery.

The effects of Na-free and of K-free solutions on the membrane potential, on tension development, and on 45Ca exchange have been investigated in rabbit ear artery. The contraction induced by Na-free solutions and the tension which develops in K-free solutions after a delay of about 1 h are both submaximal. Exposure for 4 h to K-free solutions does not affect the membrane potential, whereas Na-free solutions depolarize the cells by 10-20 mV, depending on the Na-substitute. Neither the amplitude nor the rate constant of the slowly exchanging 45Ca-fraction is affected by these experimental procedures. Substituting external Na by choline or TMA induces a transient increase of the 45Ca-efflux rate which does not occur in a Ca-free efflux medium, and which can be blocked with La. K readmission to Na-enriched tissues hyperpolarizes the cells up to -100 mV and induces a relaxation, without exerting any effect on the 45Ca efflux rate. The release of Ca from intracellular stores, induced by histamine and FCCP, and its subsequent extrusion through the plasma membrane produce a transient stimulation of the 45Ca efflux, which is not affected by the reduction of the Na gradient. The transient contraction induced by histamine in Ca-free solutions is affected in a different way by different Na substitutes. The results do not fit the Na-Ca exchange hypothesis but are consistent with an effect of the Na gradient on the passive Ca influx.

Animals↗
PubMed1977

Electro- and pharmacomechanical coupling in the smooth muscle cells of the rabbit ear artery.

A contraction of the rabbit ear artery can be induced by depolarizing the cells with a K-rich solution if Ca is present. 10(-9)-10(-6) M noradrenaline and 10(-8)-10(-7) M histamine cause a contraction of this tissue without modifying the membrane potential. If the histamine concentration exceeds 10(-7) M some depolarization of the membrane also occurs. Both noradrenaline and histamine also induce a contraction in Ca-free medium, even if La is present. None of these stimuli produces action potentials or fluctuations of the membrane potential. Besides these tonic contractions, the ear artery can also produce phasic contractions when 10 mM TEA is added to the medium. Such contractions are caused by the appearance of action potentials which are Ca dependent and which are similar to those appearing in visceral smooth muscle. A study of 45Ca fluxes has revealed that K depolarization and noradrenaline cause only a small increase in 45Ca uptake by the cells, while noradrenaline also releases cellular Ca, even in Ca-free medium. A comparison of tension development and 45Ca release induced by noradrenaline in Ca-free medium suggests that Ca extrusion could be very efficient in the rabbit ear artery and that it could play a direct role in its relaxation.

Action Potentials↗
PubMed1973

Effect of sodium and sodium-substitutes on the active ion transport and on the membrane potential of smooth muscle cells.

1. The changes of the ion content and of the membrane potential of taenia coli cells have been studied during prolonged exposure to Na-deficient solutions containing either Li or choline.2. A K-free solution containing either 71 mM-Na-71 mM-Li or 71 mM-Na-71 mM choline causes a slower loss of cellular K than a 142 mM-Na solution. In both these Na-deficient solutions the membrane hyperpolarizes to about -100 mV for periods up to 6 hr. This hyperpolarization is partially abolished by 2 x 10(-5)M ouabain.3. Replacing all extracellular Na by Li and maintaining 5.9 mM-K causes a fast loss of all Na and a progressive replacement of K by Li. These changes of the intracellular ion content are accompanied by a depolarization of the cells, suggesting that intracellular Li cannot substitute for Na in activating the ion pump.4. Exposing K-depleted cells to a K-free 71 mM-Na-71 mM-Li solution results in a ouabain sensitive transport of Na and Li against their electro-chemical gradient.5. The K-uptake by K-depleted cells from a solution containing 0.59 mM-K is increased by reducing [Na](o) to half of its normal value. This finding indicates that external Na inhibits the active Na-K exchange.6. In Na-enriched tissues half of the Na efflux is due to a ouabain insensitive Na-exchange diffusion. If Li is used as a Na substitute, the Na-Li exchange compensates for the diminution of the Na-exchange diffusion unless ouabain is added.

Animals↗
PubMed1971

Membrane potential of smooth muscle cells in K-free solution.

1. The changes of the ion content, the membrane potential and of the membrane permeability of taenia coli cells have been studied during exposure to K-free solutions. The relative value of the total membrane conductance was determined by measuring the electrotonic potential during constant current pulses with an intracellular electrode. The P(K) values were calculated from (42)K-efflux in K-free solutions.2. In solutions containing penetrating anions the cells initially depolarize. Thereafter they hyperpolarize to about - 85 mV and again depolarize after 90 min to - 5 mV. These potential changes are much smaller if large anions are used as chloride substitutes. Moreover, the final depolarization is only reached after 4-5 hr. This hyperpolarization is not inhibited by 10(-5)M ouabain.3. These potential changes are accompanied by a progressive exchange of intracellular K by Na. In solutions containing chloride or nitrate the relative value of the total membrane conductance increases to a maximal value, corresponding to the peak value of the calculated P(K). Such changes of the membrane conductance and of P(K) do not occur in K-free solutions containing large anions.4. It is proposed that the initial depolarization is probably caused by an inhibition of an electrogenic Na pump. In chloride or nitrate solution the hyperpolarization is due to an increase of the [K](i)/[K](o) ratio and to an increase of the K permeability. In the presence of large anions the hyperpolarization remains small because this increase of P(K) does not occur.

Animals↗
PubMed1971

Electrogenic sodium pump in smooth muscle cells of the guinea-pig's taenia coli.

1. The changes of the membrane potential, of the K equilibrium potential, and of the membrane conductance during K accumulation by K-depleted tissues have been studied. Three subsequent characteristic periods can be described.2. Readmission of 5.9 mM-K after complete depletion results in a rapid extrusion of Na and uptake of K, and in a rapid hyperpolarization of the cells. Initially the time course of the K equilibrium potential and the membrane potential are similar except in propionate solution. This initial period is characterized by a high membrane conductance. No change of membrane potential occurs if 10(-5)M ouabain is present.3. After 5-7 min the membrane potential becomes more negative than the K equilibrium potential. The difference between both values is larger in solutions containing propionate or in hypertonic solutions. This second phase of the recovery period is characterized by a progressive decrease of the membrane conductance.4. In a third phase both the membrane potential and the membrane resistance return to their steady-state value.5. If the external K concentration in the recovery solution is increased, the maximal hyperpolarization is less and has a shorter duration. A decrease of the temperature of the recovery solution results in a slower initial rate of repolarization and in a decrease of the maximal value of the hyperpolarization.6. These observations demonstrate the existence of an electrogenic sodium pump in smooth muscle cells during stimulation of the Na pump. An analysis of the experimental data obtained under steady-state conditions in normal Krebs solution suggests that also under these conditions an electrogenic Na pump might take part in the maintenance of the resting potential.

Animals↗