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Biomedical subjects

R Casteels

Publications and source records attributed to R Casteels.

At least 181 records · Page 10Linked to original sources
PubMed1979

The action of acetylcholine and catecholamines on an intracellular calcium store in the smooth muscle cells of the guinea-pig taenia coli.

1. The role of an intracellular Ca store in excitation-contraction coupling was studied by recording isometric tension development of thin strips (100-150 micron in diameter) of taenia coli incubated in Ca-free solution containing 2 mM-EGTA. 2. The smooth muscle cells of taenia coli do not contract during exposure to a K+-rich and Ca-free solution. However a contractile response can be elicited by acetylcholine or carbachol at concentrations exceeding 10(-6) M. These contractions are probably induced by a release of intracellular Ca. Ca is also released from the same store, although less effectively, by histamine and caffeine. 3. The amount Ca in the intracellular store, as revealed by the magnitude of the carbachol contraction in Ca-free solution, increases after contractions have been induced by high (K+)0 or by solutions containing low concentrations of carbachol. This contraction amplitude decreases after stimulation with a high concentration of carbachol. The amount of Ca in the filled store is sufficient for a near-maximal contraction. 4. The activation of beta-receptors during a K+-depolarization reduces the height of the contracture and induces a carbachol response in Ca-free solution which is higher than that obtained after a preceding K+ depolarization without isoprenaline. This observation indicates that an increased uptake of Ca into the carbachol-sensitive store contributes to the relaxing effect of beta-agonists. 5. In the tissues which have been loaded with 45Ca in a K+-depolarizing solution, a release of Ca into Ca-free solution is observed when the muscle is stimulated with carbachol, but not when it is stimulated with Ca-free high K+. The release is larger when isoprenaline was present during the loading with 45Ca. 6. The removal of Na+ from the solution exerts a complex and unexplained action on the Ca store. Substitution of Na+ by Tris+ and by K+ have similar effects. 7. It is concluded that the smooth muscle cells of the guinea-pig taenia coli have an intracellular store of Ca which participates in excitation-contraction coupling. The store is sensitive to muscarinic agonists, beta-agonists and monovalent ions, but is not affected by depolarization of the outer membrane.

Acetylcholine↗
PubMed1977

A comparative study of the calcium accumulation by mitochondria and microsomes isolated from the smooth muscle of the guinea-pig taenia coli.

The calcium uptake by mitochondria and microsomes isolated from the guinea-pig taenia coli was studied at physiological Ca2+ concentrations, buffered by Ca-EGTA mixtures. The Ca accumulation by the mitochondria was measured from the difference between the amount of Ca taken up in the presence and in the absence of a specific mitochondrial inhibitor. The Ca uptake by the microsomes was determined in a solution containing oxalate and a mitochondrial inhibitor. It was calculated from the difference in Ca uptake measured with and without ATP. By using this procedure, the necessity of extensive purification of the isolated fractions was avoided. The (Ca2+) for half-maximal transport in the mitochondria is 7 X 10(-6) M. At (Ca2+) lower than 2 X 10(-7) M, Ca is taken up in an energy-dependent way. In the microsomes the apparent Km for Ca is 7 X 10(-7) m. accumulation is still stimulated by ATP at a (Ca2+) as low as 4 X 10(-8) M. The results show that the rate of Ca uptake by the cell organelles corresponding to the microsomal vesicles is sufficiently fast to explain the speed of relaxation of the taenia coli. The results also suggest that these cell organelles are more important than the mitochondria in regulating the cytoplasmic Ca concentration.

Adenosine Triphosphate↗
PubMed1977

A study of releasable Ca fractions in smooth muscle cells of the rabbit aorta.

The distribution of Ca in the cellular compartment of smooth muscle cells of the rabbit aorta has been studied by analyzing the effect of norepinephrine, caffeine, and DNP on 45Ca exchange and on the pattern of tension development. These three substances increase the release of 45Ca from the tissue, but DNP acts more slowly than norepinephrine or caffeine. Also, the effect of norepinephrine and caffeine on tension development occurs almost immediately, while that of DNP appears only after a delay of 5 min. Study of the effect of these substances on the Ca efflux has shown that norepinephrine and caffeine act probably on the same Ca compartment, while DNP seems to act on a different compartment with a slower exchange rate. The difference between these two pools could be further demonstrated by studying Ca release after loading the tissues with tracer in either K-rich solution or in a solution with reduced [Ca]o. The K depolarization results in an excessive loading of the cells with 45Ca. Exposing these cells during the efflux procedure to a solution containing DNP causes a much larger release of 45Ca than that observed after a loading procedure in normal solution. In contrast, the release of 45Ca elicited in such tissues by norepinephrine or caffeine disappears. This disappearance is due to the prolonged increase of the Ca exchangeability induced by K depolarization. During initial exposure to PSS the increased exchangeability causes an accelerated loss of tracer from the tissue compartment on which norepinephrine and caffeine act, while the DNP sensitive compartment is not affected. It is suggested that noradrenaline and caffeine act on the same calcium pool close to the membrane and that DNP acts mainly on the mitochondria.

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↗
PubMed1977

The membrane properties of the smooth muscle cells of the rabbit main pulmonary artery.

1. The membrane potential of the smooth muscle cells of the rabbit main pulmonary artery amounts to -57 mV, the length constant of the tissue is 1.48 mm and the time constant of the membrane 182 msec. On the basis of the electrical properties of its membrane, this smooth muscle tissue is classified as a single-unit type. During outward current pulses, the membrane shows marked rectification and action potentials can never be generated.2. Tetraethylammonium (10 mM) and procaine (5 mM) depolarize the membrane and increase the membrane resistance. By studying the effect of both substances on the (42)K efflux, it could be concluded that they reduce the K-permeability of the membrane. They also suppress the rectification of the membrane and increase the length constant of the membrane. In the presence of TEA and procaine, a graded response of the membrane can be induced by outward current pulses, but overshoot potentials never occur.3. Noradrenaline, in concentrations between 2 x 10(-8) and 10(-7)M, evokes contraction without depolarizing the membrane. When the concentration is increased above 2 x 10(-7)M, noradrenaline depolarizes the membrane and reduces the membrane resistance. A study of the effect of noradrenaline on the K, Cl and Na fluxes has revealed that it increases the permeability of the membrane for these three ions.4. The tissue concentrations of Na and K are 80 and 38 m-mole/kg wet wt., respectively. The amount of Cl in the cellular compartment was measured by an extrapolation procedure and found to be 13 m-mole/kg wet wt. The extracellular space measured with [(14)C]sorbitol is 550 ml./kg wet wt. and the dry wt./wet wt. ratio 19%. The calculated equilibrium potentials for K, Na and Cl (E(K), E(Na) and E(Cl)) are -83, +59 and -26 mV, respectively. In efflux experiments under steady-state conditions, the following rate constants have been calculated: 0.092 min(-1) for Na, 0.029 min(-1) for Cl and 0.0054 min(-1) for K. The calculated value for the ratio P(Na)/P(K) was 0.22 and for P(Cl)/P(K) 0.63.5. K-free solution and 2 x 10(-6)M ouabain depolarize the cells by about 8 mV. After exposure of the cells to K-free solution, they hyperpolarize on readmission of K, suggesting that part of the membrane potential could be due to electrogenic transport of ions.6. A decrease of external Ca depolarizes the cells and increases the membrane resistance. Na-deficiency hyperpolarizes these smooth muscle cells but this procedure does not prevent the depolarization induced by Ca deficiency.

Animals↗
PubMed1977

Excitation-contraction coupling in the smooth muscle cells of the rabbit main pulmonary artery.

1. Increasing the external K concentration depolarizes the smooth muscle cells of the main pulmonary artery, and this depolarization reaches a maximal slope of 58 mV for a tenfold change of [K](o). The threshold depolarization for inducing contraction is at 4 mV and the maximal contraction is reached at a [K](o) of 58 mM.2. Noradrenaline concentrations between 2 x 10(-8)M and 10(-7)M induce tension without depolarizing the cells, but at higher concentrations noradrenaline not only elicits a large tension response but also depolarizes the cells in a dose-dependent way.3. The effect of noradrenaline on the pulmonary artery is appreciably modified by substituting sucrose for NaCl: the cells are slightly hyperpolarized and the tension response is very much reduced.4. By studying the tension response to noradrenaline in other experimental conditions which cause a small hyperpolarization of the cells, such as 5 mM-[Ca](o), 2.9 mM-[K](o) or a small depolarization, such as 11.9 mM-[K](o), it was found that a slight modification of the membrane potential can exert an important effect on the noradrenaline response.5. A simultaneous decrease of [Ca](o) and [Na](o) reduces the tension response to all noradrenaline concentrations. It was found that a reduction of [Na](o) exerts a more depressing effect than a reduction of [Ca](o). In interpreting these results we have to take into account changes of the membrane potential, of availability of Ca, and some competition between external Ca and Na.6. A study of the effect of different concentrations of noradrenaline in Krebs solutions and Ca-free solution has shown that concentrations up to 2.5 x 10(-7)M elicit contraction by increasing the Ca influx, while higher concentrations also induce a release of cellular Ca.7. Caffeine depolarizes the cells and reduces the membrane resistance. It modifies the K, Cl and Ca fluxes in the same way as noradrenaline, but it suppresses the mechanical response induced by noradrenaline.

Animals↗
PubMed1975

The influence of calcium on the electrical and mechanical activity of the guinea pig ureter.

Low calcium concentration in the external medium depolarises the membrane of smooth muscle cells of the ureter and their excitability diminishes. The Ca++ dependent oscillations of the action potential disappears, while the plateau component is more resistent. Analogous reactions are observed by the addition of Ca++ antagonists such as Lantanum or Verapramil. A high Calcium concentration produces a slight hyperpolarisation, which stabilises the membrane and enhances the spike component while decreasing the plateau component of the action potential. It is possible that several drugs act indirectly on the ureter by changing the relationship between the calcium concentration of the external versus the internal medium.

Action Potentials↗
PubMed1975

The influence of potassium on the electrical and mechanical activity of the guinea pig ureter.

Increase of the external K+ concentration depolarises the ureteral muscle membrane and induces, after a transient period of increased spontaneous activity, a tonic contraction. Tetraethylammonium, in concentrations normally required for ganglion blocking activity, does not influence the ureteral activity, but in higher doses it prolonges the duration of the action potential several times and increases the intraluminal pressure. Ouabain has only an inhibitory effect on the guinea pig ureter.

Action Potentials↗
PubMed1975

The influence of sodium on the electrical and mechanical activity of the ureter.

In Sodium-deficient solutions both the electrical and mechanical activity of the ureter are reduced. The plateau component of the action potential in the smooth muscle cell of the guinea pig ureter is more affected than the oscillations. Tetrodotoxin, which blocks the action potential in nerves, does not influence activity or conduction in the ureter. This is an important argument for the myogenic conduction of activity in this tissue.

Action Potentials↗
PubMed1975

Stimulation of 45Ca efflux from smooth muscle cells by metabolic inhibition and high K depolarization.

The characteristics of the extracellular and cellular calcium exchange in taenia coli have been studied by efflux experiments under different experimental conditions. The exchange of extracellularly bound calcium is accelerated by the presence of calcium in the external solution. If a Ca-free solution is used as washing solution, the slowly exchanging extracellular calcium also contributes appreciably to the later phase of the Ca efflux and obscures the changes of the cellular calcium exchange. There is no evidence for a Ca-Ca exchange diffusion. Most of the 45Ca bound at extracellular binding sites can be released by a 10 min exposure to 2 mM EGTA or to 10 mM La3+. This La concentration moreover largely inhibits the release of 45Ca from the cellular compartment by metabolic depletion. A release of cellular 45Ca can be induced by metabolic depletion or by K depolarization. Both procedures probably act at the same sequestering sites. However, while DNP + IAAa cts in the absence of external Ca, it is observed that K depolarization can only cause a Ca release if external Ca can enter the cells.

Adenosine Diphosphate↗
PubMed1975

Active and passive Ca2+ fluxes across cell membranes of the guinea-pig taenia coli.

The exchange of Ca between the extracellular fluid and the cellular compartment has been investigated in smooth muscle cells of taenia coli. It was found that during the initial phase of metabolic depletion by DNP + IAA, the net inwards flux of Ca amounts to 0.02 pmol cm(-2)-sec(-1). This increase might be proportional to the physiological calcium leak. The study of the relation between the inwardly directed Na gradient and the cellular Ca content has revealed that this Na gradient exerts no effect during prolonged exposure to K-free solution and a very limited effect during exposure to Na-deficient solutions. The cellular 45Ca release induced by metabolic inhibition is not affected by substituting Li or choline for Na. The supplementary calcium which enters the cells during exposure to a solution at low temperature is extruded on returning to a solution at 35 degrees C, even if the Na gradient is reversed. This finding and the effects of metabolic inhibition indicate that Ca extrusion in smooth muscle cells is a process which depends on metabolism and which is not affected by the inwardly directed Na gradient.

Adenosine Triphosphate↗