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A novel calmodulin antagonist, CGS 9343B, modulates calcium-dependent changes in neurite outgrowth and growth cone movements

KA Polak, AM Edelman, JW Wasley and CS Cohan
Journal of Neuroscience 1 February 1991, 11 (2) 534-542; DOI: https://doi.org/10.1523/JNEUROSCI.11-02-00534.1991
KA Polak
Department of Pharmacology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
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AM Edelman
Department of Pharmacology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
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JW Wasley
Department of Pharmacology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
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CS Cohan
Department of Pharmacology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
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Abstract

The neurotransmitter 5-HT alters growth cone motility and neurite elongation in neuron B19, isolated from the buccal ganglion of Helisoma trivolvis (Haydon et al., 1984). The effects of 5-HT are mediated by increases in intracellular calcium levels within the growth cones (Cohan et al., 1987). 5-HT causes a receptor-mediated depolarization of the membrane, which results in the opening of voltage-sensitive calcium channels. The resulting calcium influx decreases both the elongation rate and the total outgrowth of neurites. However, the mechanism(s) mediating these calcium-dependent changes is unclear. As many of the intracellular effects of calcium in eukaryotic cells are mediated by the calcium-binding protein calmodulin, we tested the involvement of such an interaction in the regulation of neurite outgrowth. In these experiments, a new, potent calmodulin antagonist with increased selectivity, CGS 9343B (CGS; Norman et al., 1987), was used to inhibit calmodulin activity during the application of 5-HT to neuron B19. The addition of 100 microM 5-HT to the culture medium resulted in a significant decrease in the rate of neurite elongation and total neurite outgrowth. Administration of CGS to the culture medium at a concentration (1.8 microM) equivalent to its IC50 for calmodulin inhibition completely blocked the inhibitory effects of 100 microM 5- HT, on both neurite elongation and total neurite outgrowth. CGS alone caused a slight decrease in elongation rate but had no significant effect on total outgrowth. CGS did not block 5-HT-induced electrical activity, indicating that it was not acting as a 5-HT receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

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The Journal of Neuroscience: 11 (2)
Journal of Neuroscience
Vol. 11, Issue 2
1 Feb 1991
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A novel calmodulin antagonist, CGS 9343B, modulates calcium-dependent changes in neurite outgrowth and growth cone movements
KA Polak, AM Edelman, JW Wasley, CS Cohan
Journal of Neuroscience 1 February 1991, 11 (2) 534-542; DOI: 10.1523/JNEUROSCI.11-02-00534.1991

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A novel calmodulin antagonist, CGS 9343B, modulates calcium-dependent changes in neurite outgrowth and growth cone movements
KA Polak, AM Edelman, JW Wasley, CS Cohan
Journal of Neuroscience 1 February 1991, 11 (2) 534-542; DOI: 10.1523/JNEUROSCI.11-02-00534.1991
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