scholarly journals Growth Cone Neurotransmitter Receptor Activation Modulates Electric Field-Guided Nerve Growth

1995 ◽  
Vol 171 (2) ◽  
pp. 330-339 ◽  
Author(s):  
L. Erskine ◽  
C.D. McCaig
1989 ◽  
Vol 93 (4) ◽  
pp. 723-730
Author(s):  
C.D. McCaig

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.


1989 ◽  
Vol 93 (4) ◽  
pp. 715-721
Author(s):  
C.D. McCaig

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.


1992 ◽  
Vol 12 (8) ◽  
pp. 2948-2959 ◽  
Author(s):  
MR Wood ◽  
J DeBin ◽  
GR Strichartz ◽  
KH Pfenninger

1988 ◽  
Vol 85 (14) ◽  
pp. 5001-5005 ◽  
Author(s):  
P. F. Maness ◽  
M. Aubry ◽  
C. G. Shores ◽  
L. Frame ◽  
K. H. Pfenninger

2007 ◽  
Vol 178 (1) ◽  
pp. 107-119 ◽  
Author(s):  
Zhexing Wen ◽  
Liang Han ◽  
James R. Bamburg ◽  
Sangwoo Shim ◽  
Guo-li Ming ◽  
...  

Bone morphogenic proteins (BMPs) are involved in axon pathfinding, but how they guide growth cones remains elusive. In this study, we report that a BMP7 gradient elicits bidirectional turning responses from nerve growth cones by acting through LIM kinase (LIMK) and Slingshot (SSH) phosphatase to regulate actin-depolymerizing factor (ADF)/cofilin-mediated actin dynamics. Xenopus laevis growth cones from 4–8-h cultured neurons are attracted to BMP7 gradients but become repelled by BMP7 after overnight culture. The attraction and repulsion are mediated by LIMK and SSH, respectively, which oppositely regulate the phosphorylation-dependent asymmetric activity of ADF/cofilin to control the actin dynamics and growth cone steering. The attraction to repulsion switching requires the expression of a transient receptor potential (TRP) channel TRPC1 and involves Ca2+ signaling through calcineurin phosphatase for SSH activation and growth cone repulsion. Together, we show that spatial regulation of ADF/cofilin activity controls the directional responses of the growth cone to BMP7, and Ca2+ influx through TRPC tilts the LIMK-SSH balance toward SSH-mediated repulsion.


1980 ◽  
Vol 87 (3) ◽  
pp. 546-554 ◽  
Author(s):  
R W Gundersen ◽  
J N Barrett

This study reports that chick dorsal root ganglion neurites undergo a rapid (20 min) reorientation of their direction of growth in response to nerve growth factor (NGF) concentration gradients in vitro. Dorsal root ganglia from chick embryos were explanted onto a collagen-poly-L-lysine substrate. After 24-48 h in culture, NGF gradients were applied to individual growth cones via a micropipette containing 50 biological units NGF/ml. The growth cones turned and grew toward these NGF sources. This turning response was not caused by the trophic effects of NGF on neurite initiation, survival, or growth rate. Dorsal root neurites also grew toward sources of mono- and dibutyryl cyclic adenosine monophosphate (dB cAMP), cyclic guanosine monophosphate (cGMP), and elevated calcium in the presence of the calcium ionophore A23187. These results are consistent with the hypothesis that intracellular levels of cAMP and /or cGMP and calcium may play a role in the turning response of dorsal root neurites toward NGF, but do not establish a causal relationship between the mechanisms of action of NGF, cyclic nucleotides and calcium. Total growth cone adherence to the substrate was measured using a timed microjet of perfusion medium. NGF increased the adherence of growth cones to the substrate, but caffeine and dB cAMP which also elicit the positive turning response, decreased growth cone adherence. Calcium, which did not elicit the positive turning response, produced a greater growth cone adherence to the substrate than that observed with NGF. Although these results do not rule out a role of adhesion changes in axonal turning to NGF, they show that a general increase in adherence does not correlate well with the rapid turning response observed in this study.


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