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PubMed2001

Transcription factors in mouse lung development and function.

Development of the mouse lung initiates on day 9.5 postcoitum from the laryngotracheal groove and involves mesenchymal-epithelial interactions, in particular, those between the splanchnic mesoderm and epithelial cells (derived from foregut endoderm) that induce cellular proliferation, migration, and differentiation, resulting in branching morphogenesis. This developmental process mediates formation of the pulmonary bronchiole tree and integrates a terminal alveolar region with an extensive endothelial capillary bed, which facilitates efficient gas exchange with the circulatory system. The major function of the mesenchymal-epithelial signaling is to potentiate the activity or expression of cell type-specific transcription factors in the developing lung, which, in turn, cooperatively bind to distinct promoter regions and activate target gene expression. In this review, we focus on the role of transcription factors in lung morphogenesis and the maintenance of differentiated gene expression. These lung transcription factors include forkhead box A2 [also known as hepatocyte nuclear factor (HNF)-3beta], HNF-3/forkhead homolog (HFH)-8 [also known as FoxF1 or forkhead-related activator-1], HNF-3/forkhead homolog-4 (also known as FoxJ1), thyroid transcription factor-1 (Nkx2.1), and homeodomain box A5 transcription factors, the zinc finger Gli (mouse homologs of the Drosophila cubitus interruptus) and GATA transcription factors, and the basic helix-loop-helix Pod1 transcription factor. We summarize the phenotypes of transgenic and knockout mouse models, which define important functions of these transcription factors in cellular differentiation and lung branching morphogenesis.

Amino Acid Motifs↗
PubMed1994

Distribution of synapses on two ascending interneurones carrying frequency-specific information in the auditory system of the cricket: evidence for GABAergic inputs.

Two identified cricket auditory interneurones, AN1 and AN2, were intracellularly labelled with horseradish peroxidase following physiological characterisation. The neurones, which have some structural similarities, have their somata in the prothoracic ganglion and axons that project to the brain. Although both carry auditory information, they have different response properties and participate in different types of phonotactic behaviour. Ultrathin sections from selected regions of their prothoracic arborisations were examined in the electron microscope after postembedding immunostaining for the inhibitory transmitter GABA. In the prothoracic ganglion AN1 branches only in the medial ventral association centre (mVAC) contralateral to the soma, and receives only iput synapses. Twenty-seven percent of these were made by processes immunoreactive for GABA. AN2 branches not only in mVAC on both sides of the ganglion but also in several other areas. It makes output synapses from large diameter neurites in mVAC on both sides of the ganglion as well as from neurites in more posterior regions of the neuropile. Most input synapses are received onto branches in the contralateral mVAC where about 19% were made from GABA-immunoreactive processes.

Animals↗
PubMed1985

Trigeminal-taste interaction in palatability processing.

Peripheral transection of the sensory branches of the trigeminal nerve in rats unbalanced palatability, selectively reducing the ingestive actions elicited by preferred tastes but leaving unchanged the aversive actions elicited by unpreferred tastes. The reduction in the number of positive ingestive actions occurred even though the capacity to emit these actions remained unimpaired. These findings show that there is an interaction between somatosensation and gustation in the processing of palatability.

Animals↗
PubMed2001

Effects of Cerebrolysin on the outgrowth and protection of processes of cultured brain neurons.

Cerebrolysin (Cere, EBEWE Arzneimittel, Austria), a peptidergic drug produced by a standardised enzymatic breakdown of porcine brain proteins, consists of a mixture of 75% free amino acids and 25% low molecular weight peptides (<10 k DA). Cerebrolysin was shown to protect against MAP2 loss in primary embryonic chick neuronal cultures after brief histotoxic hypoxia and in a rat model of acute brain ischemia. Since MAP2 is involved in processes like neuronal growth, plasticity and dendritic branching, we address the question whether Cere is protecting processes against degeneration in a chronic low serum (2% FCS) cell stress model and whether the spontaneous outgrowth of axon-like processes is influenced. This was accomplished by quantification of the neurite lengths of embryonic chicken telencephalon neurons after 4 and 8 days. Additionally, time-lapse video microscopy was performed to study a possible influence of Cere on the growth cone behaviour of axon-like processes. To distinguish between effects caused by the peptide fraction and the effects related to free amino acids, we used an artificial amino acid solution (AA-mix). Results demonstrate a process outgrowth promoting effect of the AA-mix and Cere after 4 DIV. After 8 days neuronal network degeneration occurred in the AA-mix treated cultures, whereas Cere treated cultures still presented a well differentiated neuronal network. Dying neurons could release factors possibly impeding neurite outgrowth and Cere was shown to increase the viability of chicken cortical neurons. Neither the addition of BDNF nor serum supplementation (5% and 10% FCS) could protect the neuronal network against degeneration after 8 DIV, although these treatments were shown to ameliorate the viability of chicken telencephalon neurons. This result together with the finding obtained using the artificial amino acid solution points to the peptide fraction of Cere to be responsible for the protection of processes against degeneration. Time-lapse studies of Cere treated cultures revealed a significant decrease of the velocities characterising random growth cone movements, which is thought to be responsible for an increase in the length of axon-like processes after 4 DIV.

Amino Acids↗
PubMed1985

Inter-odontoblastic fibres in human dentine observed by scanning electron microscopy.

Crowns of healthy premolars with closed apical foramina were fixed, resin-impregnated and freeze fractured. Fragments were critical-point dried and examined by scanning electron microscopy. Radial inter-odontoblastic fibres with a diameter of 0.1-0.7 micron were observed. Most of these radial fibres originated from the odontoblast cell body, but some of them arose from the pulp. Both of them entered the predentine at the rim of dentinal tubules and their branches formed the fibrous network of predentine. The odontoblast processes had only a few short side branches at the level of predentine. Some fibrils were observed in the mineralized intertubular dentine, as well.

Adolescent↗
PubMed2000

Oxygen supply to contracting skeletal muscle at the microcirculatory level: diffusion vs. convection.

An adequate supply of oxygen is essential for the normal function of all cells. Because skeletal muscle cells have the ability to vary their oxygen demand by over an order of magnitude on going from rest to vigorous contraction, it is important that mechanisms be in place to ensure that the supply of oxygen is maintained at sufficient levels. Microcirculation plays a critical role in this process, as the terminal branches of this intricate network of blood vessels determine the distribution of perfusion, as well as the structural framework for diffusion. The oxygen supply depends on proper functioning of both the convective and diffusive components of the transport system. Convection is responsible for the long-range, rapid transport of oxygen by bulk flow of the blood and diffusion is the efficient mechanism for transport over the short distances between capillaries and muscle cells. Convective transport is dominated by the movement of red blood cells, as virtually all the oxygen at normal haematocrit is carried inside them, reversibly bound to haemoglobin. Over the years, specialized techniques, many of them video-based, have been developed for use in intravital microscopy to measure the parameters needed to quantify convection and diffusion in both capillaries and the larger microvessels, arterioles and venules. Most of our knowledge of oxygen transport in the microcirculation of muscle pertains to the resting condition, because one must be able to visualize the structures of interest, such as microvessels and muscle cells, and the large tissue movements that occur during contraction preclude measurements during that time. In resting muscle it has been found that the arterioles are the primary site of the diffusion of oxygen from the circulation, where the oxygen is utilized by nearby muscle cells or diffuses directly to nearby venules or capillaries. Diffusive interactions among neighbouring capillaries have also been observed. In contracting muscles, microvessels observed immediately following the period of stimulation exhibit enhancements of both convective (increased flow of red blood cells) and diffusive (increased perfused capillary surface area) transport. The use of computational models in the interpretation of experimental studies is leading to an increased understanding of the processes that underlie the oxygen transport system in skeletal muscle.

Animals↗
PubMed2000

The acidic pin of RuvA modulates Holliday junction binding and processing by the RuvABC resolvasome.

Holliday junctions are four-way branched DNA structures formed during recombination, replication and repair. They are processed in Escherichia coli by the RuvA, RuvB and RuvC proteins. RuvA targets the junction and facilitates loading of RuvB helicase and RuvC endonuclease to form complexes that catalyse junction branch migration (RuvAB) and resolution (RuvABC). We investigated the role of RuvA in these reactions and in particular the part played by the acidic pin located on its DNA-binding surface. By making appropriate substitutions of two key amino acids (Glu55 and Asp56), we altered the charge on the pin and investigated how this affected junction binding and processing. We show that two negative charges on each subunit of the pin are crucial. They facilitate junction targeting by preventing binding to duplex DNA and also constrain branch migration by RuvAB in a manner critical for junction processing. These findings provide the first direct evidence that RuvA has a mechanistic role in branch migration. They also provide insight into the coupling of branch migration and resolution by the RuvABC resolvasome.

Amino Acid Sequence↗
PubMed1976

The first optic ganglion of the bee. II. Topographical relationships of the monopolar cells within and between cartridges.

The arrangement of first and second order neurons in an optic cartridge and the topographical relationships of the second order neurons within a cartridge and to groups of surrounding cartridges have been analyzed in the visual system of the bee, Apis mellifera, from light and electron microscope studies on Golgi preparations. At the level of the monopolar cell body layer, the nine retinula cell fibres of each ommatidium, the six short visual fibres arranged in a circle surrounding the three long visual fibres, become cartridges as a consequence of the appearance of the second order neurons (L-fibres) which join the R-fibre bundles. Two of the four different L-fibre types, L-1 and L-2, remain together in the centre of the cartridge throughout the lamina. The axons of the L-3 and L-4 fibres, however, have their position integrated into the circle formed by the endings of the short visual fibres. On the basis of further examination of light and especially electron microscopical Golgi material, the different L-fibres can be classified into four types which appear in each cartridge. The clear stratification in the first synaptic region (A, B and C) seems to be the best criterion for a morphological classification since such a classification necessarily also includes a functional basis. According to a naming system based on the position of the lateral processes, L-fibres with side branches in strata A, B and C are called L-1 fibres. Fibres with lateral processes in strata A and B are L-2 fibres; monopolar cell fibres with branches only in the second stratum B are L-fibres of type 3; and all monopolar cells with branches only in stratum C are called L-4 fibres. In addition to the branching pattern covering only the parent cartridge, two of the four fibre types (L-2 and L-4) have long collaterals reaching neighbouring cartridges: L-2 in stratum A and L-4 in straum C. These collaterals presumably form a substrate for lateral interactions.

Animals↗
PubMed2005

DNA binding by the substrate specificity (wedge) domain of RecG helicase suggests a role in processivity.

RecG differs from most helicases acting on branched DNA in that it is thought to catalyze unwinding via translocation of a monomer on dsDNA, with a wedge domain facilitating strand separation. Conserved phenylalanines in the wedge are shown to be critical for DNA binding. When detached from the helicase domains, the wedge bound a Holliday junction with high affinity but failed to bind a replication fork structure. Further stabilizing contacts are identified in full-length RecG, which may explain fork binding. Detached from the wedge, the helicase region unwound junctions but had extremely low substrate affinity, arguing against the "classical inchworm" mode of translocation. We propose that the processivity of RecG on branched DNA substrates is dependent on the ability of the wedge to establish strong binding at the branch point. This keeps the helicase motor in contact with the substrate, enabling it to drive dsDNA translocation with high efficiency.

Amino Acid Sequence↗
PubMed1997

Developing human biliary system in three dimensions.

BACKGROUND: In the development of the human biliary system, although the extrahepatic bile ducts develop from the embryonic hepatic diverticulum, there is increasing evidence to suggest that the intrahepatic bile ducts originate within the liver from the ductal plate. The ductal plate develops as a sheath of primitive biliary epithelium in the mesenchyme along the portal vein branches. Through an orderly process of selection and deletion, the ductal plate is remodelled into the adult system of anastomosing tubular bile ducts. The ductal plate remodelling process occurs at the porta hepatis between 11 and 13 weeks of gestation and progresses towards the periphery of the liver. METHODS: In this project, for the first time, we have used computerised three-dimensional reconstruction techniques to visualise the developing human biliary system. Paraffin-embedded tissue from eight human embryos or fetuses between 5.5 and 16 weeks of gestation were serially sectioned, and their images were aligned, digitised, and used for three-dimensional reconstruction. RESULTS AND CONCLUSIONS: Three-dimensional images of the extrahepatic and the intrahepatic biliary systems were obtained, and the following conclusions were drawn. (1) The intrahepatic biliary system, both at the porta hepatis and within the liver, developed from the ductal plate through a consistent pattern of remodelling. (2) Prior to the remodelling process, the ductal plate was of similar morphology irrespective of site and gestation. (3) The extrahepatic biliary system was in direct luminal continuity with the developing intrahepatic biliary system throughout gestation and did not show the presence of a "solid stage" in any of the embryos or fetuses studied.

Bile Ducts, Extrahepatic↗
PubMed1984

Axonal and dendritic development of substantia gelatinosa neurons in the lumbosacral spinal cord of the rat.

In the present study, developing neurons of the substantia gelatinosa (SG) are examined at short interval sequential stages from 15 days of gestation through 20 days postpartum. Rapid Golgi preparations are utilized to examine axonal and dendritic development and toluidine blue preparations are employed to study the overall growth pattern of SG cells by measuring changes in mean cell body area. Results show that there are two maturation periods, which involve two separate groups of SG neurons. The sequence and pattern of development for each group is different. The first period occurs prenatally and involves the axonal and dendritic development of presumptive projection and propriospinal neurons. In classical terminology, these cells can be classified as limiting, large and small central, and transverse cells. These neurons have axons that enter the white matter and their dendritic arbors develop through a relatively simple process of elongation and branching. The second maturation period occurs postnatally and involves the development of presumptive nonprojection intrinsic neurons that have axons which remain within the gray matter. These neurons are identified as islet, stalk, inverted stalklike, and vertical cells. Unlike projection or propriopinal neurons, the intrinsic nonprojection neurons sprout numerous short, beaded dendrites that radiate from the cell body in a starlike fashion. Starshaped cells undergo a metamorphosis involving a rearrangement of dendrites along adult dendritic patterns. Measurements taken from toluidine blue preparations indicate that the nonprojection intrinsic population makes up the greatest percentage of SG neurons, as evidenced by a marked increase in the size of the average SG nerve cell during the second maturation period.

Animals↗
PubMed1990

Musculotopic organization of the facial motor nucleus in Macaca fascicularis: a morphometric and retrograde tracing study with cholera toxin B-HRP.

Morphometric and retrograde tracing methods were used to determine the location and number of motoneurons innervating individual facial muscles in Macaca fascicularis. Intramuscular injections of the cholera toxin B subunit-horseradish peroxidase conjugate produced discrete labeling patterns in the ipsilateral facial motor nucleus with good definition of somata and their processes. The facial nucleus extended rostrocaudally in the pons for about 2 mm, varying in shape and cross-sectional area along this axis. Motoneurons were clustered in subnuclei, but their boundaries were not sharp and they were not segregated by fiber bundles. The length, number, and area of subnuclei varied with rostrocaudal location. Retrograde labeling patterns revealed that individual muscles were innervated by longitudinal columns of motoneurons with each muscle region represented at all rostrocaudal levels of its column. The columns began at different rostrocaudal levels and varied in length. Columns for closely related muscles, such as the orbicularis oris and mentalis of the lower lip, tended to overlap, whereas columns for disparate muscles, such as the perioral and orbital, did not overlap. The dendritic processes of most motoneurons branched extensively among several different columns or subnuclei. Some dendrites extended outside of the nucleus into the surrounding tegmentum. Mean soma diameter (10.4-42.2 microns) was distributed unimodally, reflecting the absence of gamma motoneurons and lack of muscle spindles in the facial muscles. Large and small motoneurons were found in all regions of the nucleus, but the largest ones were located caudally and innervated muscles of the upper and lower lip. The perioral muscles also had more neurons, longer columns, and a lower cell density than the other muscle groups examined. These features may reflect the functions of the perioral muscles in facial expression and vocalization.

Animals↗
PubMed1991

Distribution, laminar location, and morphology of tectal neurons projecting to the isthmo-optic nucleus and the nucleus isthmi, pars parvocellularis in the pigeon (Columba livia) and chick (Gallus domesticus): a retrograde labelling study.

Retrograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L), fluorogold, fast blue, rhodamine labelled microspheres, and horseradish peroxidase (HRP) was employed to study the distribution, laminar location within the optic tectum, and morphology of tectal cells projecting upon the isthmo-optic nucleus (ION) and the nucleus isthmi, pars parvocellularis (Ipc), in the pigeon and chick. Following injections into the ION, all retrograde markers labelled tecto-ION neurons and their dendrites in the ipsilateral tectum. The cells were located within a relatively narrow band at the border between layers 9 and 10 of the stratum griseum et fibrosum superficiale (SGFS). Retrogradely labelled neuronal somata were different in both dendritic branching and shape; however, tecto-ION neurons generally possessed non-spiny radially oriented and multi-branched dendrites. The apical processes extended into the retino-recipient layers (2-7) of the SGFS and basal dendrites extended into layers 12-14 of the SGFS. Positive neuronal somata were observed throughout the rostro-caudal extent of the optic tectum. The average distance between adjacent tecto-ION neurons varied from one region to another. Specifically, retrogradely labelled cells were more numerous in the caudal, lateral, and ventral tectum, and less numerous at rostro-dorsal levels. Approximately 12,000 tecto-ION neurons were labelled within the ipsilateral optic tectum following either PHA-L or fluorescent dye injections. While the regional distribution of tecto-Ipc neurons was not examined, the morphology indicated that the cells had a single radially oriented dendritic process. Therefore, the apical dendrites are more restricted than those of tecto-ION cells. Moreover, the dendrites were spiny and arborized within layers 3, 5, and 9 of the ipsilateral optic tectum. The axon of tecto-Ipc cells arise from the apical process as a shepherd's crook and descend into the deep layers of the optic tectum. These results indicate that 1) tecto-ION and tecto-Ipc neurons are possibly monosynaptically activated by retinal input, 2) tecto-ION neurons are heterogeneous in morphology, and 3) there is a differential distribution of the tecto-ION neurons throughout the rostro-caudal extent of the optic tectum, suggesting a greater representation of the caudo-ventral portion of the optic tectum within the ION. The discussion primarily concerns the organization of the retino-tecto-ION-retinal circuit in light of the distribution and morphology of tecto-ION neurons within the optic tectum.

Animals↗
PubMed1992

Development of commissural neurons in the embryonic rat spinal cord.

Little is known about the development of the various populations of interneurons in the mammalian spinal cord. We have utilized the lipid-soluble tracer DiI in fixed tissue to study the migration and dendritic arborization of spinal neurons with axons in the ventral commissure in embryonic rats. Crystals of DiI were placed in various locations in the thoracic spinal cord in order to label commissural neurons within the dorsal horn, intermediate zone, and ventral horn at E13.5, E15, E17, and E19. Seven different groups of commissural interneurons are present in the spinal cord by E13.5. Migration is relatively simple with groups occupying a position along the dorsoventral axis roughly corresponding to their position of origin along the neuroepithelium. By E15, commissural cells are near their final locations and exhibit characteristic morphology. One striking feature is the tendency of cells with similar morphology to cluster in distinct groups. By E19, at least 18 different types of commissural interneurons can be identified on morphological grounds. Although the situation is complex, some generalities about dendritic morphology are apparent. Commissural neurons located in the dorsal horn are small and have highly branched dendrites oriented along the dorsoventral axis. In more ventral regions, commissural neurons are larger and possess dendritic arbors oriented obliquely or parallel to the mediolateral axis with long dendrites extending toward the lateral and ventral funiculi. The number of primary dendrites of most groups is set by E15 and dendritic growth occurs in the transverse plane by lengthening and branching of these primary processes. This study demonstrates that a large number of classes of commissural interneurons can be recognized on the basis of characteristic morphologies and locations within the dorsal horn, intermediate zone and ventral horn of the embryonic rat spinal cord. This finding is consistent with the fact that commissural neurons project to many different targets and mediate a variety of different functions. The demonstration that dendritic arbors of spinal interneurons with characteristic morphologies can be conveniently labelled with DiI should prove useful in future studies on the development of specific circuits in the mammalian spinal cord.

Animals↗
PubMed2006

21st century neontology and the comparative development of the vertebrate skull.

Classic neontology (comparative embryology and anatomy), through the application of the concept of homology, has demonstrated that the development of the gnathostome (jawed vertebrate) skull is characterized both by a fidelity to the gnathostome bauplan and the exquisite elaboration of final structural design. Just as homology is an old concept amended for modern purposes, so are many of the questions regarding the development of the skull. With due deference to Geoffroy-St. Hilaire, Cuvier, Owen, Lankester et al., we are still asking: How are bauplan fidelity and elaboration of design maintained, coordinated, and modified to generate the amazing diversity seen in cranial morphologies? What establishes and maintains pattern in the skull? Are there universal developmental mechanisms underlying gnathostome autapomorphic structural traits? Can we detect and identify the etiologies of heterotopic (change in the topology of a developmental event), heterochronic (change in the timing of a developmental event), and heterofacient (change in the active capacetence, or the elaboration of capacity, of a developmental event) changes in craniofacial development within and between taxa? To address whether jaws are all made in a like manner (and if not, then how not), one needs a starting point for the sake of comparison. To this end, we present here a "hinge and caps" model that places the articulation, and subsequently the polarity and modularity, of the upper and lower jaws in the context of cranial neural crest competence to respond to positionally located epithelial signals. This model expands on an evolving model of polarity within the mandibular arch and seeks to explain a developmental patterning system that apparently keeps gnathostome jaws in functional registration yet tractable to potential changes in functional demands over time. It relies upon a system for the establishment of positional information where pattern and placement of the "hinge" is driven by factors common to the junction of the maxillary and mandibular branches of the first arch and of the "caps" by the signals emanating from the distal-most first arch midline and the lamboidal junction (where the maxillary branch meets the frontonasal processes). In this particular model, the functional registration of jaws is achieved by the integration of "hinge" and "caps" signaling, with the "caps" sharing at some critical level a developmental history that potentiates their own coordination. We examine the evidential foundation for this model in mice, examine the robustness with which it can be applied to other taxa, and examine potential proximate sources of the signaling centers. Lastly, as developmental biologists have long held that the anterior-most mesendoderm (anterior archenteron roof or prechordal plate) is in some way integral to the normal formation of the head, including the cranial skeletal midlines, we review evidence that the seminal patterning influences on the early anterior ectoderm extend well beyond the neural plate and are just as important to establishing pattern within the cephalic ectoderm, in particular for the "caps" that will yield medial signaling centers known to coordinate jaw development.

Animals↗
PubMed1980

Ultrastructural differentiation and synaptogenesis in aggregating rotation cultures of rat cerebral cells.

Cerebral cortices from fetal rats were dissociated into single cells by either trypsinization or mechanical sieving. Then the cells were allowed to form aggregates in rotation cultures. At 7, 14, 21, 28, and 35 days, aggregates were processed for electron microscopic study of morphological differentiation with special emphasis on synaptogenesis. Whether the tissue was initially dissociated by trypsin treatment or by mechanical sieving, the aggregating cultures did not exhibit any apparent differences in ultrastructural differentiation and synaptogenesis. At day 7, most neurons were immature and the extracellular space was large. Cell processes had not yet branched extensively but did contain numerous microtubules. A few immature synapses were observed. Astrocytes and oligodendrocytes displayed many of their typical cytological features. At day 14, dendritic spines had developed, some of which formed axodendritic spinous synapses. Multilayered myelin sheaths were tightly wrapped around axons. At day 21, synapses appeared mature and their number per unit area was maximal. The extracellular space had greatly decreased. At this age, asymmetrical synapses had increased approximately sixfold, whereas symmetrical synapses increased only fourfold when compared with the 7-day-old aggregates. Multifocal degeneration became apparent at 28 days and was accompanied by a significant decline in the number of synapses.

Animals↗
PubMed1985

Central connections of Limulus ventral photoreceptors revealed by intracellular staining.

We stained the central terminations of Limulus ventral photoreceptors by intracellular injection of cobalt chloride into the cell bodies. Axons of these photoreceptors enter the protocerebrum via the ventral optic nerve and pass to the medulla. As they reach the surface of the medullar neuropil they branch profusely in fine processes with intermittent varicosities. Each axonal arborization covers about 0.01-0.02 mm2 of this surface immediately adjacent to the medullar ganglion cell layer. Each point on the surface of the medullar neuropil receives, on the average, input from about 6 ventral photoreceptor axons.

Axons↗
PubMed1998

Nimodipine suppresses preferential reinnervation of mouse soleus muscles by slow alpha-motoneurons.

Denervation of mouse soleus muscle followed by self-reinnervation causes a significant increase in slow twitch (type I) muscle fiber content, suggesting preferential reinnervation by slow alpha-motoneurons. Since intracellular Ca2+ influences both axonal elongation rate and branching, we examined the process of self-reinnervation in mouse soleus muscles in the presence of the L-type Ca2+ channel blocker nimodipine. Soleus muscles in both control and experimental animals were denervated by crushing the soleus nerve where it enters the muscle. Experimental animals received a daily i.p. injection of a 0.1% nimodipine solution beginning 4 days prior to denervation and ending 2 weeks postdenervation. At 2 months postdenervation reinnervated and contralateral muscles from both control and experimental animals were sectioned and histochemically stained for myosin ATPase to determine the percentage of slow twitch fibers in the muscles. It was found that, in agreement with previous experiments, untreated reinnervated muscles had a significantly higher percentage of slow twitch fibers than did their contralateral controls (91.3 versus 74. 6%). However, in nimodipine-treated animals only a small, but not statistically significant, difference between reinnervated and contralateral control muscles was observed (76.5 versus 72.8%). These results suggest that Ca2+ influx through L-type calcium channels in growing neurites may play a role in the outcome of the reinnervation process.

Animals↗