Energetics and regulation of crossbridge states in mammalian smooth muscle

Conclusion On the basis of measurements of the high energy phosphate usage associated with different mechanical states, as well as the degree of myosin light chain phosphorylation and mechanical properties, information has been gained concerning the existence and regulation of different crossbridge states in smooth muscle. Although incomplete, a general operational scheme is shown in figure 5. At very low intracellular calcium concentrations, actin and myosin are dissociated, as shown by a loss of resistance to stretch in resting muscles. At somewhat higher intracellular calcium concentrations in atonic, resting muscles, crossbridges can attach and be manifest mechanically as an increased resistance to stretch without ATP-driven crossbridge cycling and active force production. When the muscle is activated, intracellular calcium increases further, the light chains of myosin are phosphorylated through the calcium-calmodulin activation of myosin light chain kinase, actin-activated myosin ATPase activity increases and crossbridges cycle. Calcium also appears to modulate the ATPase activity and the rate of cycling of the phosphorylated crossbridge. The crossbridge cycling rate is highest during force development and slows with time as maximum isometric force is maintained reflecting a change in the rate at which phosphorylated crossbridges cycle. This may result from a decrease in the intracellular free calcium concentration with continued stimulation. During relaxation, the intracellular calcium concentration decreases, there is net dephosphorylation of the myosin light chains, the rate at which phosphorylated crossbridges cycle slows further with a gradual return to the attached, but non-cycling state or the detached state.     

Ion adsorption and excitation

Résumé Les données expérimentales suggèrent que la surface fonctionnelle du nerf (c'est-à-dire la couche à travers laquelle le potentiel de repos se manifeste) est située à une certaine distance de la surface morphologique de l'axone et sa localisation à chaque moment dépend de létat fonctionnel de la cellule. D'après un calcul fondé sur la durée du «spike» de l'axone du Calmar, la surface fonctionnelle de la cellule serait à 5 µ de la surface morphologique.     

Ion adsorption and excitation II

Résumé Une façon simple de formuler le potentiel de repos de l'axone géant du Calmar est présentée. L'équation est fondée sur une démonstration antérieure prouvant que pendant l'excitation les cations importants forment une seule couche à la surface fonctionnelle du nerf. La formule est employée pour calculer la distribution du chlorure. Le résultat est en accord avec les valeurs expérimentales publiées.     

Muscle spindles in the rat diaphragm

Zusammenfassung Elektrophysiologische Registrierungen afferenter Impulse des Nervus phrenicus aus dem isolierten Rattenzerchfell wurden durch eine histologische Untersuchung des Zwerchfelles unterbaut. Das Vorkommen von durchschnittlich 3 Muskelspindeln in jeder Zwerchfellhälfte wurde nachgewiesen.     

Regulation and electric excitation of enzyme membranes in vitro]

Enzyme membranes can be activated or inhibited by applying continuous or alternating electrical fields. The field can modify the transport or reaction term of the transport-reaction by action on the displacement of charged species including those giving pH effects or inducing volume flows. A first experimental example is given: the progressive supression of the inhibition of hexokinase by the product when increasing alternating fields are applied. In the same way the apparent optimal pH approaches that of the soluble enzyme. In addition to its theoretical and practical implications electrical regulation can lead to the monitoring of enzyme reaction-driven mechanochemical fibers.     

Dopamine-induced relaxation in human pulmonary arteries

Dose-dependent relaxations were induced by dopamine in human pulmonary arteries that had been contracted with prostaglandin F2 alpha without alpha-adrenergic blocking agents. The dopamine-induced relaxation was inhibited by haloperidol and fluphenazine, but not by domperidone, suggesting that this relaxation was mediated via DA1 receptors.     

Experimental and theoretical work on excitation and excitation-contraction coupling in the heart

A combination of experimental and theoretical work has been used to investigate the movements of calcium during cardiac excitation. In addition to calcium entry through several types of calcium channel, calcium efflux occurs to balance the entry during each cycle of activity. Measurements of net membrane calcium movements have been made with the right time resolution by Don Hilgemann in Los Angeles by investigating fast extracellular calcium transients. This work shows that, in mammalian cardiac cells, net calcium exit occurs quite early during repolarization and is nearly complete by the time the resting potential is re-established. These results correlate very well indeed with measurements made in the Oxford laboratory of calcium-activated inward current in single cardiac myocytes. Both approaches are consistent with the view that calcium efflux occurs largely through the sodium-calcium exchange process. Modelling of this process in equations developed recently with Dario DiFrancesco, Susan Noble and Don Hilgemann succeeds in reproducing both the ionic current changes and the fast extracellular calcium transients.     

Laser-induced excitation of fluorescein isothiocyanate in the immunofluorescence

Zusammenfassung Methode für die Anregung des FITC in der Immunofluoreszenz mit Argon-Laser-Licht, die eine sehr starke Fluoreszenz ermöglicht. Diese Methode wird in dem FTA-ABS-Test für Syphilis benutzt.     

Longitudinal stress relaxation in the canine aorta

Résumé On a mesuré chez le chien la relaxation de la tension longitudinale en fonction de la déformation dans l'aorte, l'artère rénale et l'artère mésentérique supérieure. Dans les déformations équivalent à celles du vaisseau in vivo, la relaxation de la tension longitudinale est mise en relation avec les effets combinés de la teneur en collagène et des muscles lisses.

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This work was supported by Program Project Research Grant No. HL 07762 from the Public Health Service.     

The action of cycloheximide on the action potential and protein synthesis in medullatedXenopus axons

Summary Cycloheximide depresses maximum rate of change in membrane potential observed during the rising phase of the action potential in single medullated axons ofXenopus. Time course of depression is independent of cycloheximide concentration over a range that almost completely inhibits leucine incorporation into axonal proteins.     

Blood pressure and impairment of endothelium-dependent relaxation in spontaneously hypertensive rats

Summary Correlation between hypertension and impairment of endothelium-dependent relaxation was demonstrated using aortae from certain strains of rats with various levels of spontaneous hypertension. It was also observed that the impairment of endothelium-dependent relaxation is the secondary change due to hypertension, and the level and duration of hypertension is the determinant factor of the impairment.     

Muscle specific structural differences in piscine muscle glycogens

Summary Piscine red muscles are rich in glycogen content. Structurally white muscle glycogens have one glucosidal unit more in their external branches than the red muscles.The author wishes to thank the CSIR, New Delhi for the award of a Junior Research Fellowship.     

Blood pressure and impairment of endothelium-dependent relaxation in spontaneously hypertensive rats

Correlation between hypertension and impairment of endothelium-dependent relaxation was demonstrated using aortae from certain strains of rats with various levels of spontaneous hypertension. It was also observed that the impairment of endothelium-dependent relaxation is the secondary change due to hypertension, and the level and duration of hypertension is the determinant factor of the impairment.     

Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle

Vascular smooth muscle tone is controlled by a balance between the cellular signaling pathways that mediate the generation of force (vasoconstriction) and release of force (vasodilation). The initiation of force is associated with increases in intracellular calcium concentrations, activation of myosin light-chain kinase, increases in the phosphorylation of the regulatory myosin light chains, and actin-myosin crossbridge cycling. There are, however, several signaling pathways modulating Ca²⁺ mobilization and Ca²⁺ sensitivity of the contractile machinery that secondarily regulate the contractile response of vascular smooth muscle to receptor agonists. Among these regulatory mechanisms involved in the physiological regulation of vascular tone are the cyclic nucleotides (cAMP and cGMP), which are considered the main messengers that mediate vasodilation under physiological conditions. At least four distinct mechanisms are currently thought to be involved in the vasodilator effect of cyclic nucleotides and their dependent protein kinases: (1) the decrease in cytosolic calcium concentration ([Ca²⁺]c), (2) the hyperpolarization of the smooth muscle cell membrane potential, (3) the reduction in the sensitivity of the contractile machinery by decreasing the [Ca²⁺]c sensitivity of myosin light-chain phosphorylation, and (4) the reduction in the sensitivity of the contractile machinery by uncoupling contraction from myosin light-chain phosphorylation. This review focuses on each of these mechanisms involved in cyclic nucleotide-dependent relaxation of vascular smooth muscle under physiological conditions.     

Muscle proteinase activities during compensatory growth and atrophy

Specific activities of cathepsins B and D, but not H, increased in both the tenotomized gastrocnemius and functionally overloaded soleus muscles, thus correlating with previously reported increases in protein degradation. Subsequent denervation of the overloaded soleus caused an additive increase in proteolysis, suggesting a possible greater lability of proteins in this muscle.     

Muscle proteinase activities during compensatory growth and atrophy

Summary Specific activities of cathepsins B and D, but not H, increased in both the tenotomized gastrocnemius and functionally overloaded soleus muscles, thus correlating with previously reported increases in protein degradation. Subsequent denervation of the overloaded soleus caused an additive increase in proteolysis, suggesting a possible greater lability of proteins in this muscle.     

Failure of opioids to affect excitation and contraction in isolated ventricular heart muscle

Summary The opioid agonists morphine (selective for -receptors) and ethylketocyclazocine (selective for kappa-receptors), at concentrations evoking strong effects in neuronal structures, did not significantly affect the configuration of the intracellularly recorded action potential and the force of contraction in ventricular heart muscle isolated from guinea pigs, rabbits and man. These results suggest that any changes of heart functions in vivo in response to opioid-like drugs are probably not mediated postsynaptically at the myocardial cell membrane but rather presynaptically, influencing the release of noradrenaline and/or acetylcholine from the nerve terminals.     

Failure of opioids to affect excitation and contraction in isolated ventricular heart muscle

The opioid agonists morphine (selective for mu-receptors) and ethylketocyclazocine (selective for kappa-receptors), at concentrations evoking strong effects in neuronal structures, did not significantly affect the configuration of the intracellularly recorded action potential and the force of contraction in ventricular heart muscle isolated from guinea pigs, rabbits and man. These results suggest that any changes of heart functions in vivo in response to opioid-like drugs are probably not mediated postsynaptically at the myocardial cell membrane but rather presynaptically, influencing the release of noradrenaline and/or acetylcholine from the nerve terminals.     

Isometric relaxation in rat myocardium: load dependence and influence of caffeine

When caffeine plus calcium is added to the perfusing medium, isometric relaxation of rat myocardium is no longer affected by length changes occurring during the twitch. The dependence of isometric relaxation on the initial muscle length is still present and more pronounced after caffeine addition.     

Isometric relaxation in rat myocardium: Load dependence and influence of caffeine

Summary When caffeine plus calcium is added to the perfusing medium, isometric relaxation of rat myocardium is no longer affected by length changes occurring during the twitch. The dependence of isometric relaxation on the initial muscle length is still present and more pronounced after caffeine addition.