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C D McCaig

Publications and source records attributed to C D McCaig.

At least 37 records · Page 2Linked to original sources
PubMed1993

Raised cyclic-AMP and a small applied electric field influence differentiation, shape, and orientation of single myoblasts.

The effects of the adenyl cyclase activator forskolin and of a small applied electric field on the differentiation, morphology, and orientation of processes from single Xenopus myoblasts has been studied. Forskolin promoted myoblast differentiation (elongation from spherical cells) and induced extra process growth, such that normally bipolar muscle cells possessed on average five or six processes. Both events appeared to depend on elevated levels of cyclic AMP, since they were mimicked by another adenyl cyclase activator, cholera toxin, and by two membrane-permeable analogues of cyclic AMP. By contrast, the forskolin analogue dideoxyforskolin, which does not elevate adenyl cyclase levels, was without effect. Forskolin-stimulated differentiation depended on new protein synthesis, while excess process production required both new protein synthesis and intact microfilaments. Both control and forskolin-treated myoblasts developed a long axis perpendicular to an applied electric field. In addition, many processes on forskolin-treated muscle cells turned to grow toward the cathode; untreated processes did not turn to either pole. Since this nerve-like orientation behavior was inhibited by a protein synthesis inhibitor, the expression of an integral component of galvanotropism may be stimulated by forskolin treatment and by raised cyclic AMP levels in myoblasts.

Animals↗
PubMed1992

The effects of melanocortins and electrical fields on neuronal growth.

The effects of the neuropeptide molecules, adrenocorticotrophic hormone or alpha-melanocyte stimulating hormone, on various parameters of in vitro nerve growth, have been studied in the presence and absence of a small applied electric field. Striking effects on rates of nerve growth occurred. Selected concentrations of either substance alone, produced a three- to fourfold increase in nerve growth rate; other concentrations were inhibitory. The applied electric field alone increased rates of growth threefold. Further augmented rates of growth were seen when either neuropeptide was present simultaneously with an applied field. Under these latter conditions, galvanotropic (cathodal) orientation persisted, while nerve branching was suppressed. Given the clinical interest in melanocortin-stimulated nerve regeneration, perhaps a combined electrical and neuropeptide approach would be warranted.

Adrenocorticotropic Hormone↗
PubMed1992

Electric field-induced orientation of rat hippocampal neurones in vitro.

Rat hippocampal neurones in primary culture exhibited directional growth in response to DC electric fields. Neurites lay perpendicular to the field after exposure to 28, 80 or 219 mV/mm but there was no orientation effect at 9 mV/mm or in unexposed control cultures. Fields that evoked perpendicular responses also reduced the number of cathode-facing neurites. Orientation was the same for neurite initiation sites and the direction of overall neurite growth.

Animals↗
PubMed1991

Electrical fields, nerve growth and nerve regeneration.

The presence of voltage gradients within developing and damaged tissues led to the notion that the resultant electrical fields provide instructional cues to cells. Field effects on avian and amphibian neurones in vitro include increased differentiation, turning of neurites towards the cathode, increased rate of growth towards the cathode, resorption of anodefacing neurites, increased branching and increased filopodial activity. Electric fields enhance regeneration of damaged PNS and CNS neurones in animals as diverse as lampreys, frogs, rats and guinea-pigs, but the mechanisms by which fields produce their effects are not understood. Further examination of the interaction of fields with intracellular elements, such as the cytoskeleton and second messenger systems, may offer some insight.

Animals↗
PubMed1991

Factors influencing perpendicular elongation of embryonic frog muscle cells in a small applied electric field.

The mechanism controlling the perpendicular elongation of embryonic muscle cells exposed to a small applied electric field has been studied using a pharmacological approach. Inhibition of the inositol phosphate second messenger system, of calcium entry and of microfilament polymerisation all prevented perpendicular elongation. A model involving strengthened adhesion asymmetrically along the cathodal-facing side of round myoblasts and incorporating the above requirements is proposed to explain electric field-induced perpendicular differentiation. Some asymmetry of organelles is described also, with ribosomes, yolk granules and actin filaments all predominantly found on the anodal side of myoblasts.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Nerve branching is induced and oriented by a small applied electric field.

Nerve branching is controlled by intrinsic and extrinsic cues, one of which may be a small applied electric field. Lateral processes were induced by passing current through a micropipette placed at 90 degrees to the shaft of a developing nerve. The appearance of processes was a polarised event with a large majority arising from the cathodal facing side of nerves. Whilst an electric field alone may promote branching, the presence of dimethyl sulfoxide (DMSO) or the ganglioside GM1 enhanced branching of developing nerves. It is likely that an applied electric field promotes microtubule disassembly locally along the neurite shaft and that this can lead to a polarised rearrangement of the neuronal cyto-skeleton. It is suggested that the use of an applied electric field in conjunction with these pharmacological agents might enhance nerve regeneration in vivo.

Animals↗
PubMed1990

Nerve growth in a small applied electric field and the effects of pharmacological agents on rate and orientation.

The rate of growth and orientation of embryonic Xenopus nerves exposed to pharmacological agents, to an applied electric field or to both simultaneously were studied. The adenyl cyclase activator forskolin (100 microM) induced a threefold increase in the rate of elongation, as did an electric field alone. Together, their effect in augmenting rate of growth was additive, but only at a concentration of 50 microM forskolin. The normal pattern of faster growth towards cathode than anode was not present in nerves treated with the lectin concanavalin A, which also inhibits normal turning behaviour towards the cathode. Nerve orientation towards the cathode and augmented rates of growth were found in the presence of forskolin or ganglioside GM1. It is suggested that a combined approach of drug treatment and an applied electric field may be useful in promoting nerve regeneration.

Animals↗
PubMed1989

Nerve growth in the absence of growth cone filopodia and the effects of a small applied electric field.

Nerve orientation may involve a biasing of the distribution of tension at the growth cone. Chemical and electrical guidance cues cause more filopodia to appear on one side of the growth cone and this may determine turning behaviour. In a small applied electric field, filopodia predominate on the cathodal side of the growth cone and nerves turn towards the cathode. Removing all filopodia by treatment with cytochalasin D did not prevent nerves from continued slow growth and nerves still oriented towards the cathode. It is concluded that nerves can perform some types of orienting behaviour in the complete absence of filopodia.

Actins↗
PubMed1989

Studies on the mechanism of embryonic frog nerve orientation in a small applied electric field.

The mechanism of nerve orientation in an applied electric field has been investigated using a number of pharmacological agents. Galvanotropism may depend on redistribution within the plasma membrane of integral membrane proteins (IMP); blocking this with concanavalin A inhibited orientation. Orientation may depend also on an influx of Ca2+; Co2+ and La3+ blockade of calcium channels inhibited turning in an electric field. Organic blockers of calcium channels did not influence orientation, suggesting that L-type Ca2+ channels may not be present at the growth cone. Procedures that may induce asymmetric entry of Ca2+ on the anodal side of cells caused a reversal of normal galvanotropism, with growth directed towards the anode. This may implicate local levels of cytoplasmic Ca2+ within the growth cone in controlling turning behaviour. An asymmetric distribution of filopodia precedes and may predict the direction of nerve growth in an electric field. Various pharmacological agents perturbed the distribution of filopodia in such a way that this did not reflect subsequent orientation. It is suggested that, normally, local Ca2+ increases and an asymmetry of filopodia operate together in determining orientation, but that filopodial activity is subordinate to and can be overriden by local Ca2+ levels in the growth cone. In addition, two of the drug treatments markedly increased rates of nerve growth, which may be of importance in nerve regeneration.

Animals↗
PubMed1987

Embryonic somatic nerve destruction with beta-bungarotoxin.

The effects and time course of a single injection of beta-bungarotoxin into E14 rat embryos were examined with an electron-microscopic study of development of the internal intercostal somatic nerve. Within 24 h of injection, axons in this nerve became swollen and fused at points along their length. By 48 h after injection no component of the nerve remained in distal segments of ribcage; complete loss of axons and components of the nerve sheath from proximal regions took slightly longer. At later times, no trace of peripheral nerve axons, Schwann cells or elements of the nerve sheath remained. beta-Bungarotoxin applied on E17 destroyed developing axons in a similar manner, but the perineurium remained in place, and axons regenerated within the original nerve trunk. The study confirms that sensory and motor neurons are much less able to survive axon degeneration on E14 than after the major period of normal cell death (which is nearly over by E18), and that the maintenance and continued development of the perineurium during E14-E16 depends on the presence of peripheral nerve axons.

Animals↗
PubMed1987

Spinal neurite reabsorption and regrowth in vitro depend on the polarity of an applied electric field.

Retraction and regrowth of frog neural tube neurites have been studied in vitro in control cultures and in the presence of a small, continuously applied electrical field. In control cultures, some degree of retraction was seen in 39% of neurites while 7% were reabsorbed completely. Reabsorption of anodal-facing neurites was at least twice as common, with 67% showing some retraction and 17% almost totally reabsorbed. Cathodal-facing neurites were spared from retraction. Following extreme reabsorption of anodal-facing neurites, reversal of the electric field promoted regeneration in 47% (9/19) of cases studied. growth cone morphology also was determined by the polarity of the applied field. Anodal-facing growth cones had fewer filopodia than cathodal-facing growth cones sharing the same cell body. Field reversal induced a polarity-specific change in filopodia number on individual growth cones: a shift from anodal to cathodal increased filopodia numbers and vice versa. Some possible mechanisms involved and the significance of these results are discussed.

Animals↗
PubMed1986

Myoblasts and myoblast-conditioned medium attract the earliest spinal neurites from frog embryos.

A study was made of the capacity of newly segmented somites, unsegmented mesoderm and medium conditioned by each of these tissues to attract the growth of the earliest spinal neurites from the neural tube of Xenopus laevis in tissue culture. When presented with segmented somitic myoblasts or sheets of skin, spinal neurites grew selectively towards the somitic myoblasts. Neurites were not attracted specifically to somitic myoblasts from their own rostrocaudal level. A variable proportion of myoblasts from unsegmented caudal mesoderm differentiated and elongated in co-culture with neural tube and skin. These myoblasts also attracted neural outgrowths, but only if present in sufficient numbers. An agar slab containing medium conditioned by the presence of segmented myoblasts for 1 day attracted neurite outgrowths. A source of medium conditioned by the presence of undifferentiated, unsegmented myotomal mesoderm alone did not attract neurite outgrowths. Nerve growth factor (NGF) at a range of concentrations in the agar source (500-10,000 ng/ml) did not attract the earliest neurite outgrowths. It is concluded that the earliest skeletal myoblasts from Xenopus laevis embryos may attract neural outgrowths by releasing a soluble factor. Myoblasts may have to develop to the stage of somite segmentation before secretion of such an agent begins. The release of a myoblast-derived factor so early in development may assist directed nerve growth in vivo.

Animals↗
PubMed1986

Dynamic aspects of amphibian neurite growth and the effects of an applied electric field.

The dynamics of growth of earliest spinal neurites from Xenopus laevis have been studied in vitro in the presence and absence of an applied d.c. electric field. Control and cathode-directed neurites grew at a rate of about 30 micron/h: growth of anodal-facing neurites was 8 times slower. Periods of arrested growth were common in cultured neurones; these lasted 2-3 times longer in an applied electric field. The likelihood and the severity of neurite reabsorption was greatest in neurites directed towards the anode. Many neurites turned to direct their growth towards the cathode. As this happened their rate of growth increased 2-3-fold. The electric field further shaped neurite morphology by increasing the number of filopodia at the growth cone and by increasing the number of cytoplasmic spines along a neurite shaft. The electric field induced an asymmetry in the distribution of these cytoplasmic projections; greater numbers being found on the cathodal-facing than on the anodal-facing side. Implications of these data for nerve growth in development and in regeneration are discussed.

Animals↗
PubMed1986

Myoblasts and notochord influence the orientation of somitic myoblasts from Xenopus laevis.

The orientation of developing myoblasts extending a bipolar axis in the presence of explanted myoblasts or whole notochord has been studied in vitro. Myoblasts tended to elongate perpendicular to the lines of diffusion of substances from these tissues. A slow-release source of agar impregnated with medium conditioned by segmented somitic myoblast or notochord also caused myoblasts to elongate perpendicular to the lines of diffusion from the source. Medium conditioned by neural tube cells or unsegmented mesoderm cells did not influence the orientation of myoblasts. It is concluded that somites and notochord release diffusible substances in vitro which are capable of directing the orientation of developing myoblasts. In vivo, a somite-derived material could play a role in determining the direction of myoblast elongation in the presomitic mesoderm. An interaction between somite and notochord-derived secretions could influence the rotation of presomitic myoblasts to form a segmented somite.

Animals↗
PubMed1986

Electric fields, contact guidance and the direction of nerve growth.

Nerve orientation in response to electrical guidance cues in one direction and contact guidance cues in an orthogonal direction has been studied. Where neurites had a free choice between following contact guidance cues or electrical cues, the direction of nerve growth was determined predominantly by the vector of the applied electric field.

Animals↗
PubMed1985

A potential difference across mouse ovarian follicle.

A small potential difference (antrum positive) has been measured with fine-tipped glass microelectrodes across the epithelial cell layers of the mouse ovarian follicle wall. As ovulation approached the potential in the antrum became more positive compared to the outside. Metabolic inhibitors and locally active hormones also altered the potential difference. The ionic basis and the significance of the potential difference are unknown.

Alprostadil↗