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Oxygen free radicals and calcium homeostasis in the heart.

Many experiments have been done to clarify the effects of oxygen free radicals on Ca2+ homeostasis in the hearts. A burst of oxygen free radicals occurs immediately after reperfusion, but we have to be reminded that the exact levels of oxygen free radicals in the hearts are yet unknown in both physiological and pathophysiological conditions. Therefore, we should give careful consideration to this point when we perform the experiments and analayze the results. It is, however, evident that Ca2+ overload occurs when the hearts are exposed to an excess amount of oxygen free radicals. Though ATP-independent Ca2+ binding is increased, Ca2+ influx through Ca2+ channel does not increase in the presence of oxygen free radicals. Another possible pathway through which Ca2+ can enter the myocytes is Na(+)-Ca2+ exchanger. Although, the activities of Na(+)-K+ ATPase and Na(+)-Ca2+ exchanger. Although, the activities of Na(+)-H+ exchange are inhibited by oxygen free radicals, it is not known whether intracellular Na+ level increases under oxidative stress or not. The question has to be solved for the understanding of the importance of Na(+)-Ca2+ exchange in Ca2+ influx process from extracellular space. Another question is 'which way does Na(+)-Ca2+ exchange work under oxidative stress? Net influx or efflux of Ca2+?' Membrane permeability for Ca2+ may be maintained in a relatively early phase of free radical injury. Since sarcolemmal Ca(2+)-pump ATPase activity is depressed by oxygen free radicals, Ca2+ extrusion from cytosol to extracellular space is considered to be reduced. It has also been shown that oxygen free radicals promote Ca2+ release from sarcoplasmic reticulum and inhibit Ca2+ sequestration to sarcoplasmic reticulum. Thus, these changes in Ca2+ handling systems could cause the Ca2+ overload due to oxygen free radicals.

Adenosine Triphosphate↗

Oxygen free radicals and calcium homeostasis in the heart.

Many experiments have been done to clarify the effects of oxygen free radicals on Ca2+ homeostasis in the hearts. A burst of oxygen free radicals occurs immediately after reperfusion, but we have to be reminded that the exact levels of oxygen free radicals in the hearts are yet unknown in both physiological and pathophysiological conditions. Therefore, we should give careful consideration to this point when we perform the experiments and analyze the results. It is, however, evident that Ca2+ overload occurs when the hearts are exposed to an excess amount of oxygen free radicals. Through ATP-independent Ca2+ binding is increased, Ca2+ influx through Ca2+ channel does not increase in the presence of oxygen free radicals. Another possible pathway through which Ca2+ can enter the myocytes is Na(+)-Ca2+ exchanger. Although, the activities of Na(+)-K+ ATPase and Na(+)-H(+) exchange are inhibited by oxygen free radicals, it is not known whether intracellular Na(+) level increases under oxidative stress or not. The question has to be solved for the understanding of the importance of Na(+)-Ca2+ exchange in Ca2+ influx process from extracellular space. Another question is 'which way does Na(+)-Ca2+ exchange work under oxidative stress? Net influx or efflux of Ca2+?' Membrane permeability for Ca2+ may be maintained in a relatively early phase of free radical injury. Since sarcolemmal Ca(2+)-pump ATPase activity is depressed by oxygen free radicals, Ca2+ extrusion from cytosol to extracellular space is considered to be reduced. It has also been shown that oxygen free radicals promote Ca2+ release from sarcoplasmic reticulum and inhibit Ca2+ sequestration to sarcoplasmic reticulum. Thus, these changes in Ca2+ handling systems could cause the Ca2+ overload due to oxygen free radicals.

Animals↗

Molecular mechanisms of cell-cell signaling by the Spemann-Mangold organizer.

We review how studies on the first Spemann-Mangold organizer marker, the homeobox gene goosecoid, led to the discovery of secreted factors that pattern the vertebrate embryo. Microinjection of goosecoid mRNA formed secondary axes and recruited neighboring cells. These non-cell autonomous effects are mediated in part by the expression of secreted factors such as chordin, cerberus and Frzb-1. Unexpectedly, many of the molecules secreted by the Spemann-Mangold organizer turned out to be antagonists that bind growth factors in the extracellular space and prevent them from binding to their receptors. The case of chordin is reviewed in detail, for this molecule has provided biochemical insights into how patterning by Spemann's organizer can be regulated by diffusion and proteolytic control. The study of the BMP-binding repeats of Chordin, which are present in many extracellular proteins, may provide a new paradigm for how cell-cell signaling is regulated in the extracellular space not only in embryos, but also in adult tissues.

Amino Acid Sequence↗

Endocytosis in rat intrahepatic bile duct epithelial cells of horseradish peroxidase injected into the common bile duct or the portal vein.

While recent data in intrahepatic bile duct epithelial cells (IBDECs) isolated from normal rat liver have established their ability to undergo endocytosis, few studies have assessed endocytosis in IBDECs in situ. Thus, to clarify the activity of IBDECs in situ on macro-molecules in bile and blood, we injected horseradish peroxidase (HRP) into either the common bile duct or the portal vein, and determined its intracellular distribution by electron microscopic cytochemistry. Successful retrograde injection into the common bile duct was achieved by resection of the liver surface so as to avoid HRP leakage from the bile duct on injection. IBDECs internalized HRP through both the apical and basolateral plasma membranes. By quantitative analysis, counting the number of HRP-positive vesicles in the cells, apical endocytosis was found more active than basolateral. HRP internalized through the apical membrane was either routed to the acid phosphatase-positive lysosomes for degradation or to extracellular space for transcytosis. HRP through the basolateral membrane was transferred to the organelles having lipid inclusion, which were expected to be lysosomes negative for acid phosphatase. Our results suggest that IBDECs in situ are actively engaged in endocytosis for degradation of macromolecules in bile and blood, and possibly engaged in the excretion of macromolecules into extracellular space.

Animals↗

Relations between slow extracellular potential changes, glial potassium buffering, and electrolyte and cellular volume changes during neuronal hyperactivity in cat brain.

The aim of this investigation is to estimate the contribution of spatial glial K+ buffer currents to extracellular K+ homeostasis during enhanced neuronal activity. Neuronal hyperactivity was induced by electrical stimulation of the cortical surface or the ventrobasal thalamic nuclei of cats (5-50 Hz, 0.1-0.2 ms, two to three times threshold stimulation intensity, 5-20 s). The accompanying slow field potential changes were recorded simultaneously across the grey matter with vertical assemblies of eight micropipettes glued 300 microns apart. Using the Poisson equation, the amplitudes of the underlying current sources and sinks were calculated. The current source densities depended on the depth of recording, frequency, strength, and duration of the stimulation. Current sinks, corresponding to a removal of 0.1-0.5 mmoles of monovalent cations per liter of brain tissue and second from the extracellular space, were observed in middle cortical layers, whereas sources appeared at superficial and deeper sites. These sinks and sources might represent K+ moved across glial membranes by spatial buffer currents. The consequences of glial buffer currents of this magnitude were investigated with model calculations. It turned out that measurements of electrolyte and volume changes of the extracellular space (Dietzel et al. Exp. Brain Res. 40:432-439, 1980; Exp. Brain Res. 46:73-84, 1982) could only partially be explained by spatial buffer currents of this magnitude. Comparison of the calculated values with intracellular measurements in neurons and glial cells (Coles et al. Ann. N.Y. Acad. Sci. 481:303-317, 1986; Ballanyi et al. J. Physiol. 382:159-174, 1987) suggests that spatial buffering combines with an approximately equimolar KCl transport and, depending on the preparation, also K+/Na+-exchange across glial membranes.

Action Potentials↗

Ultrastructural changes associated with renin secretion from the juxtaglomerular apparatus of mice.

Thin sections and freeze-fracture replicas were used to investigate the ultrastructural changes associated with renin secretion from the juxtaglomerular part of the afferent arteriole of male mice. Adrenalectomized animals in which renin secretion was stimulated by furosemide application and bleeding were also studied. Exocytosis of mature electron-dense granules was found in all experimental groups. Before extrusion, the region of granule facing the cell membrane changed, with vesicular and/or stacked membrane-like profiles and a small local protrusion of the granule membrane appearance of. Concomitantly, punctuate sites of fusion between the cell and granule membranes were observed. Later, unaltered amorphous, and altered membrane-like granule content was released from omega-shaped cavities into the extracellular space. In stimulated animals the alteration and extrusion of several closely apposed granules was reminiscent of compound exocytosis. Coated pits were frequently seen, suggesting specific retrieval of the former granule membrane. The collapsing silhouette of a depleted granule very rarely took the form of a saccule whose narrow membrane-bounded neck was continuous with the extracellular space. Observed were two additional events by which active and inactive renin may be released. Small electron-lucent vacuoles of undetermined origin fused with the cell membrane and, in stimulated kidneys, some epithelioid cell processes disintegrated. However, the interpretation of the related ultrastructural phenomena was uncertain.

Adrenalectomy↗

Monoamine metabolism in the striatum of the rat brain during drug infusion into the nucleus accumbens.

Studies on conscious Sprague-Dawley rats using intracerebral dialysis in live animals combined with high-performance liquid chromatography with electrochemical detection showed that administration of apomorphine into the nucleus accumbens decreased the levels of dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the extracellular space of the dorsal striatum throughout the observation period and produced a transient reduction in the level of homovanillic acid in the dialysate from this structure. The studies demonstrated that reversible exclusion of the nucleus accumbens with procaine produced a transient increase in the levels of dopamine metabolites, without an increase in serotonin metabolites, in the extracellular space of the dorsal striatum. These results demonstrate that the nucleus accumbens affects dopamine metabolism in the striatum, this being mediated by the dopamine-reactive system in the nucleus accumbens.

3,4-Dihydroxyphenylacetic Acid↗

On the characteristics of alcohol-induced liver enlargement and its possible hemodynamic consequences.

Chronic consumption of alcohol leads to an increase in liver weight, primarily due to an increase in hepatocyte volume. About 50-60% of such an increase is due to an increase in intracellular water. Accumulation of intracellular K+ osmotically accounts for about one half of the increase in intracellular water, while an increase in soluble proteins plays only a minor role in such an increase in cell volume. The increase in intracellular water is accompanied by a relative reduction in water in the extracellular space, probably due to compression of the extracellular volume by the enlarged hepatocytes. It is suggested that such an increase in hepatocyte size, with an attending reduction of the extracellular volume, results in an increased resistance to blood flow through the liver and thus in an increase in portal pressure. In alcoholics, portal and intrahepatic pressure correlate with cell size both in cirrhotics (r = 0.79) and in non-cirrhotics (r = 0.74), thus suggesting that cell enlargement plays a major role in the production of portal hypertension in the alcoholic.

Alcoholism↗

Activation-dependent cumulative depletions of extracellular free calcium in guinea pig atrium measured with antipyrylazo III and tetramethylmurexide.

We have used a spectrophotometric method to monitor mean free extracellular calcium concentrations in isolated left atria of guinea pigs via extracellular application of the calcium-sensitive absorption dyes, antipyrylazo III and tetramethylmurexide. Exchange of extracellular free calcium with the bathing medium takes several minutes and closely parallels contractile response in this preparation. Under conditions favoring a rapid positive force staircase response during repetitive stimulation after a long rest period (2-10 minutes), cumulative depletions of extracellular calcium can clearly be differentiated from motion artifact due to muscle movement by multiple-wavelength spectrophotometry. Responses of similar magnitude and characteristics are obtained with both dyes employed. In the presence of 10(-7) M isoproterenol, the mean extracellular calcium concentration falls by at least 5% (0.25-0.8 mM total calcium concentration) in four beats at 0.5 Hz; extracellular calcium replenishes during rest with an apparent t1/2 of 25-60 seconds. A 10-minute pretreatment with 10(-8) M ryanodine greatly reduces the contraction force and motion artifact of the first beat after a rest period, whereby the magnitude of depletion response to one post-rest stimulation is increased 2- to 3-fold. With further ryanodine treatment, the magnitude of depletion responses remains stable, and the rate of calcium replenishment during rest increases many-fold. After ryanodine treatment and 10(-7) M isoproterenol, at least 10% of total dye accessible calcium (0.25-1.0 mM) is lost during two to five rapid stimulations, and returns to the extracellular space within 20 seconds of rest. Cumulative extracellular calcium depletion responses are strongly suppressed by 10(-6) M nifedipine. Cumulative depletion responses are also inhibited by 10 mM caffeine, whereby contraction and corresponding motion artifacts are increased at post-rest stimulation.

Animals↗

Influence of osmolality on seizure amplitude and propagation in the rat dentate gyrus.

We tested the role of changes in extracellular space on synchronization and propagation of epileptiform activity in the dentate gyrus in vitro by manipulating the osmolality of the perfusing solution. Increasing the osmolality reduced the amplitude of the population spikes and slowed the propagation of the epileptiform activity. Decreasing the osmolality had the opposite effect. Assuming there were significant changes in the size of the extracellular space, and therefore the ease with which ephaptic interactions can occur, these results support the hypothesis that ephaptic interactions play a role in the synchronization and propagation of epileptic activity in the dentate gyrus.

Animals↗

Exocytosis of arginine-specific ADP-ribosyltransferase and p33 induced by A23187 and calcium or serum-opsonized zymosan in chicken polymorphonuclear leukocytes.

Exocytosis is a common phenomenon in neutrophil functions. We earlier reported the co-localization of arginine-specific ADP-ribosyltransferase [EC 2.4.2.31] and its target protein p33 (mim-1 protein) in cytoplasmic granules in chicken polymorphonuclear leukocytes (so-called heterophils) [Mishima, K., Terashima, M., Obara, S., Yamada, K., Imai, K., and Shimoyama, M. (1991) J. Biochem. 110, 388-394]. In the present study, we obtained evidence that the transferase and p33 were released into the extracellular space by the stimulus of calcium ionophore A23187 or serum-opsonized zymosan, but scarcely by phorbol myristate acetate (PMA) or N-formyl-Met-Leu-Phe (fMLP), thereby indicating the co-localization of the transferase and p33 in the azurophilic granules, and not in specific granules. [32P]ADP-ribosylation of p33 occurred in the extracellular space, induced by the stimulus of A23187 or opsonized zymosan in the presence of [32P]NAD. Our findings are interpreted to mean that heterophil transferase and p33 may be involved in neutrophil functions during processes of inflammation.

ADP Ribose Transferases↗

Processing of chromogranin B in bovine adrenal medulla. Identification of secretolytin, the endogenous C-terminal fragment of residues 614-626 with antibacterial activity.

Chromogranins constitute a family of acidic soluble proteins widely distributed in endocrine cells and neurons. Chromogranin A, the major soluble component in bovine adrenal medullary secretory granules in chromaffin cells, has been shown to be actively processed to peptide fragments [Metz-Boutigue, M. H., Garcia-Sablone, P., Hogue-Angeletti, R. & Aunis, D. (1993) Eur. J. Biochem. 217, 247-257]. In the present paper, the structural features of the proteolytic degradation mechanism of chromogranin B/secretogranin I have been characterized with regard to the possible function of this protein as a precursor of biologically active peptides. Chromogranin-B-derived fragments present in bovine chromaffin granules were identified by microsequencing after separation by two-dimensional gel electrophoresis or high-performance liquid chromatography. A similar approach was performed to characterize chromogranin-B-derived fragments released into the extracellular space from depolarized bovine cultured chromaffin cells. In chromogranin B, 18 cleavage sites were identified along the protein chain and chromogranin B/secretogranin I fragments were generated by proteolytic attack at both the N-terminus and C-terminus. A major fragment corresponding to residues 614-626 of the C-terminal sequence, was identified in the extracellular space; this peptide was found to share sequence and structural similarities with the lytic domain of cecropins and, as expected from this similarity, to display potent antibacterial properties. Endogenous and synthetic peptides were active on Micrococus luteus, killing bacteria in the micromolar concentration range. The synthetic peptide slows the growth of Bacillus megaterium and was inactive towards Escherichia coli. In addition, the synthetic peptide was unable to induce hemolytic activity. This antibacterial function might be of biological significance in the neuroendocrine system of living organisms. We propose to name this peptide secretolytin.

Adrenal Medulla↗

Influence of NH(4)CI on polarized release of endogenous protein degradation products and on morphology in LLC-PK(1) cells.

Increased renal ammoniagenesis is thought to be a causative factor for renal hypertrophy which occurs in several disorders accompanied by metabolic acidosis. We studied the influence of ammonia on the polarized release of degradation products of endogenous proteins in LLC-PK(1) cells. Release of acid-soluble radioactivity to the extracellular space decreased under the influence of NH(4)Cl with a remarkable transient reduction of basolateral release. Electron microscopically NH(4)Cl-treated cells showed numerous enlarged lysosomes suggesting an accumulation of incompletely degraded cytoplasmatic material in the lysosomal compartment. We conclude that split products of lysosomal degradation of endogenous proteins are preferentially transported to the extracellular space via the basolateral plasma membrane.

Ammonium Chloride↗

Continuous measurement of 47Ca2+ uptake during and after hypoxia in rabbit myocardium.

Whereas the changes of calcium influx and net calcium content in the myocardium have been described during ischemia, less is known of the changes that occur during and after hypoxia. In this study calcium uptake was measured with 47Ca2+, a high energy gamma emitter, calcium efflux with both 47Ca2+ and 45Ca2+, and extracellular space with 51Cr-EDTA. The experimental preparation was the isolated but arterially perfused interventricular septum of the rabbit. Temperature was 32 degrees C. Hypoxia in the absence of substrate caused a fall in developed tension and rise in resting tension. After 30 min, recovery on reoxygenation was incomplete. During hypoxia without substrate small changes of the extracellular space were associated with changes of mechanical function. Calcium efflux did not alter. Calcium influx decreased during the initial 30 min, but after 60 min a small increase was evident. The tissue content of 51Cr-EDTA only increased after prolonged hypoxia, suggesting that the increase of calcium influx at this time was due to nonspecific damage to the cell membrane. On reoxygenation calcium efflux was unaltered, but a large incrase of calcium influx occurred without an associated influx of 51Cr-EDTA. The influx of calcium on reoxygenation appears, therefore, to be caused by a relatively specific abnormality of the calcium transport system and not by generalized destruction of the cell membrane.

Animals↗

A mathematical model of ion movements in grey matter during a stroke.

The development of cytotoxic oedema during a stroke consists in cell swelling and shrinking of the extracellular space. This phenomenon is triggered by ion movements through voltage-gated channels, exchangers and pumps. During ischaemia, sodium, calcium and chloride enter the neurons whereas potassium and glutamate are expelled out of the cells. A mathematical model is proposed to represent the long-term dynamics of membrane potentials, cell volumes and ionic concentrations in intracellular and extracellular spaces during a stroke and to study the influence of each ionic current on cell swelling. The model relies on electrophysiological mechanisms and takes into account the behaviour of two types of cells: neurons and also astrocytes known to play a key role in the excitotoxic process in grey matter. The results obtained when a severe or a moderate ischaemia is simulated are consistent with those observed in the in vitro and in vivo experiments. As this model appears to be robust, it is used to perform illustrative simulations aimed at studying the effect of some channel blockers on cell swelling. This approach may help to explore new therapeutic strategies in order to reduce stroke damage.

Astrocytes↗

Ceramide signalling: regulatory role in cell proliferation, differentiation and apoptosis in human epidermis.

The stratum corneum of vertebrates is a major structural compartment that provides mechanical protection and prevents skin desiccation. The water barrier function of the stratum corneum was first reported in 1944, and this was shown later to be associated with multilayered lipid lamellae localized in the extracellular spaces. The major lipid components isolated from the cornified epidermal layers are ceramides, which belong to the class of sphingolipids, cholesterol and free fatty acids; their biosynthesis is in tight relationship with the cutaneous barrier function. In studies in which the barrier is artificially disturbed, lipid biosynthesis is found to be directly regulated by barrier permeability. As mentioned above, the ceramides involved in this process are located in the extracellular spaces of the upper epidermal layers, whereas sphingomyelin, the most common sphingolipid, is an integral part of the bilayer plasma membrane of the keratinocytes. During the last few years, however, increasing evidence has shown that sphingolipids may also take part in cell signalling, and the term 'sphingomyelin cycle' has been coined to describe this novel path-way of signal transduction. Intracellular messengers of the sphingomyelin cycle are ceramides as the products of an agonist-stimulated sphingomyelin hydrolysis. Increased levels of intracellular ceramides induce cell differentiation and/or apoptosis and reduce cell proliferation. In contrast to the extracellular barrier-forming ceramides which are complex partly O-acylated species containing long-chain fatty acids, intracellular signal-transducing ceramides are not O-acylated and have acyl chain lengths of 16 and 18 carbon atoms. We present here a review of our present knowledge on the sphingomyelin cycle as a possible signal transduction pathway in the human epidermis. We discuss the common origin of extracellular ceramides constituting the lipid barrier and of intracellular ceramides generated by agonist-stimulated sphingomyelin hydrolysis and serving as second messengers. A summary of alterations in sphingolipid metabolism and lipid composition of the epidermis in diseased skin is also given and the possible use of different sphingolipids for therapy is envisaged.

Apoptosis↗

Pathfinding by growth cones of commissural interneurons in the chick embryo spinal cord: a light and electron microscopic study.

To investigate putative axonal guidance mechanisms used by commissural interneurons in the chick embryo spinal cord, we have examined growth cone morphology, the microenvironment through which the growth cones advance, and interactions between growth cones and their surroundings. Growth cones of both early and late developing commissural interneurons were examined. The growth cones were visualized by injection of either horseradish peroxidase (HRP) or the fluorescent dye Di-I. Unlabelled growth cones as well as HRP-labelled growth cones were also examined by electron microscopy. The early developing growth cones project circumferentially without fasciculation until they reach the region of the longitudinal pathway in the contralateral ventral funiculus (CVF). In their trajectory towards the floor plate, axons exhibited elaborate growth cones with filopodia and lamellipodia. They projected between processes of neuroepithelial cells within abundant extracellular spaces. Upon arrival at the ipsilateral ventral funiculus, growth cones did not appear to contact preexisting longitudinal axons. Within the floor plate, the growth cones were less complex and lacked long filopodia and exhibited bulbous or varicose shapes with short processes. Electron microscopic observations of the floor plate at this stage revealed that there was only a small amount of extracellular space and that the basal portion of the floor plate cells were directionally oriented (polarized) in the transverse plane. It is of particular interest that contacts between growth cones and the basement membrane in the floor plate were often observed. When the growth cones reached the contralateral ventrolateral region, they again exhibited an elaborate morphology. Close contacts between growth cones and the preexisting contralateral longitudinal axons were observed. Growth cones advancing in the contralateral longitudinal pathway exhibited various shapes and were observed to contact other axons and processes of neuroepithelial cells. Most of the later developing growth cones of commissural cells exhibited lamellipodial shapes irrespective of their location along the circumferential trajectory. Electron microscopic observations revealed that these late developing growth cones always contacted or fasciculated with preexisting axons and that the cellular environment through which they grow is oriented in such a way that the growth cones appear to be guided in specific directions. Growth cones entering the CVF exhibited more elaborated shapes with ramified lamellipodia that made multiple contacts with preexisting longitudinal axons. The present results indicate that differential axonal guidance mechanisms may be employed along the pathway followed by spinal commissural interneurons and that axons and growth cones projecting along this pathway at different developmental stages employ different mechanisms for pathfinding and guidance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Pallial oviduct of Pomacea canaliculata (Gastropoda): ultrastructural studies of the parenchymal cellular types involved in the metabolism of perivitellins.

Seasonal variations in the morphology of the parenchymal mass and function of the albumen gland/capsule gland complex have been studied in Pomacea canaliculata, together with the cellular types involved in the synthesis and secretion of perivitellin fluid components. The two major parenchymal cell types, albumen secretory cells (AS) and labyrinthic cells (LC), undergo seasonal variations throughout the annual reproductive cycle, which is divided into three periods. Both cellular types show maximal development and structural complexity during the reproductive period (spring and summer). AS cells have a well-developed Golgi complex and rough endoplasmic reticulum and their secretory granules show electron-dense particles of about 20 nm (probably galactogen). These cells are uniquely involved in ovorubin and PV2 perivitellin synthesis and their secretory granules are the single storage site for these two major perivitellins, as revealed by immunoelectron microscopy. AS also possess calcium deposits that infiltrate the cytoplasmic matrix. The luminal surfaces of LC exhibit long cilia intermingled with sparce short microvilli. Basally, the plasma membrane shows deep irregular folds that extend through the cytoplasm up to the subapical region. Calcium deposits infiltrate the cytoplasm and accumulate in the extracellular space of the basal labyrinth. Nerve terminals seem to be involved in the regulation of parenchymal cell secretion. At the post-reproductive period, AS markedly change their aspect following the release of most of the secretory granules into the acinar lumen. LC decrease in volume, the number of their cilia decreases, their cytoplasmic folds are much thinner and their extracellular spaces lack calcium particles. At the pre-reproductive period (winter), AS and LC recover and prepare for the subsequent period.

Animals↗