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Potassium current development and its linkage to membrane expansion during growth of cultured embryonic mouse hippocampal neurons: sensitivity to inhibitors of phosphatidylinositol 3-kinase and other protein kinases.

Hippocampal pyramidal neurons express three major voltage-dependent potassium currents, I sub(A), I sub(D), and I sub(K). During hippocampal development, I sub(A), the rapidly activating and inactivating transient potassium current, is detected soon after pyramidal neurons can be morphologically ide... Full description

Journal Title: The Journal of neuroscience : the official journal of the Society for Neuroscience August 15, 1998, Vol.18(16), pp.6261-6278
Main Author: Wu, R L
Other Authors: Butler, D M , Barish, M E
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0270-6474
Link: http://search.proquest.com/docview/80056190/?pq-origsite=primo
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title: Potassium current development and its linkage to membrane expansion during growth of cultured embryonic mouse hippocampal neurons: sensitivity to inhibitors of phosphatidylinositol 3-kinase and other protein kinases.
format: Article
creator:
  • Wu, R L
  • Butler, D M
  • Barish, M E
subjects:
  • Animals–Physiology
  • Cell Membrane–Pharmacology
  • Cells, Cultured–Cytology
  • Electric Conductivity–Embryology
  • Enzyme Inhibitors–Physiology
  • Hippocampus–Embryology
  • Mice–Cytology
  • Neurons–Drug Effects
  • Phosphatidylinositol 3-Kinases–Physiology
  • Potassium–Antagonists & Inhibitors
  • Protein Kinase Inhibitors–Physiology
  • Enzyme Inhibitors
  • Protein Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Potassium
ispartof: The Journal of neuroscience : the official journal of the Society for Neuroscience, August 15, 1998, Vol.18(16), pp.6261-6278
description: Hippocampal pyramidal neurons express three major voltage-dependent potassium currents, I sub(A), I sub(D), and I sub(K). During hippocampal development, I sub(A), the rapidly activating and inactivating transient potassium current, is detected soon after pyramidal neurons can be morphologically identified. Appearance of I sub(A) in developing pyramidal neurons is dependent on contact with cocultured astroglial cells; cultured pyramidal neurons not in contact with astroglial cells have reduced membrane area and I sub(A) (). We have examined intracellular signaling pathways that could contribute to the regulation of I sub(A) development by probing developing pyramidal neurons with kinase inhibitors. We observed that exposure to LY294002 or wortmannin, inhibitors of phosphatidylinositol (PI) 3-kinase, reduced somatic cross-sectional area, neurite outgrowth, whole-cell capacitance, I sub(A) amplitude and density (amplitude normalized to membrane area), and immunoreactivity for Kv4.2 and/or Kv4.3 (potassium channel subunits likely to be present in the channels carrying I sub(A)). In contrast, exposure to ML-9 or KN-62, inhibitors of myosin light chain kinase or Ca super(2+)-calmodulin-dependent protein kinase II (CaMKII), reduced membrane area and I sub(A) amplitude but did not affect I sub(A) density or Kv4.2/3 immunoreactivity to the same extent as inhibitors of PI 3-kinase. Unexpectedly, exposure to bisindolymaleimide I or calphostin C, inhibitors of protein kinase C (PKC), did not affect membrane area or potassium current development. Our data suggest that PI 3-kinases regulate both A-type potassium channel synthesis and plasmalemmal insertion of vesicles bearing these potassium channels. CaMKII appears to regulate fusion of channel-bearing vesicles with the plasmalemma and myosin light chain kinase to regulate centripetal transport of channel-bearing vesicles from the Golgi. We further suggest that astroglial cells exert their influence on pyramidal neuron development through activation of PI 3-kinases.
language: eng
source:
identifier: ISSN: 0270-6474
fulltext: fulltext
issn:
  • 02706474
  • 0270-6474
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titlePotassium current development and its linkage to membrane expansion during growth of cultured embryonic mouse hippocampal neurons: sensitivity to inhibitors of phosphatidylinositol 3-kinase and other protein kinases.
creatorWu, R L ; Butler, D M ; Barish, M E
contributorWu, R L (correspondence author) ; Wu, R L (record owner)
ispartofThe Journal of neuroscience : the official journal of the Society for Neuroscience, August 15, 1998, Vol.18(16), pp.6261-6278
identifierISSN: 0270-6474
subjectAnimals–Physiology ; Cell Membrane–Pharmacology ; Cells, Cultured–Cytology ; Electric Conductivity–Embryology ; Enzyme Inhibitors–Physiology ; Hippocampus–Embryology ; Mice–Cytology ; Neurons–Drug Effects ; Phosphatidylinositol 3-Kinases–Physiology ; Potassium–Antagonists & Inhibitors ; Protein Kinase Inhibitors–Physiology ; Enzyme Inhibitors ; Protein Kinase Inhibitors ; Phosphatidylinositol 3-Kinases ; Potassium
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descriptionHippocampal pyramidal neurons express three major voltage-dependent potassium currents, I sub(A), I sub(D), and I sub(K). During hippocampal development, I sub(A), the rapidly activating and inactivating transient potassium current, is detected soon after pyramidal neurons can be morphologically identified. Appearance of I sub(A) in developing pyramidal neurons is dependent on contact with cocultured astroglial cells; cultured pyramidal neurons not in contact with astroglial cells have reduced membrane area and I sub(A) (). We have examined intracellular signaling pathways that could contribute to the regulation of I sub(A) development by probing developing pyramidal neurons with kinase inhibitors. We observed that exposure to LY294002 or wortmannin, inhibitors of phosphatidylinositol (PI) 3-kinase, reduced somatic cross-sectional area, neurite outgrowth, whole-cell capacitance, I sub(A) amplitude and density (amplitude normalized to membrane area), and immunoreactivity for Kv4.2 and/or Kv4.3 (potassium channel subunits likely to be present in the channels carrying I sub(A)). In contrast, exposure to ML-9 or KN-62, inhibitors of myosin light chain kinase or Ca super(2+)-calmodulin-dependent protein kinase II (CaMKII), reduced membrane area and I sub(A) amplitude but did not affect I sub(A) density or Kv4.2/3 immunoreactivity to the same extent as inhibitors of PI 3-kinase. Unexpectedly, exposure to bisindolymaleimide I or calphostin C, inhibitors of protein kinase C (PKC), did not affect membrane area or potassium current development. Our data suggest that PI 3-kinases regulate both A-type potassium channel synthesis and plasmalemmal insertion of vesicles bearing these potassium channels. CaMKII appears to regulate fusion of channel-bearing vesicles with the plasmalemma and myosin light chain kinase to regulate centripetal transport of channel-bearing vesicles from the Golgi. We further suggest that astroglial cells exert their influence on pyramidal neuron development through activation of PI 3-kinases.
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titlePotassium current development and its linkage to membrane expansion during growth of cultured embryonic mouse hippocampal neurons: sensitivity to inhibitors of phosphatidylinositol 3-kinase and other protein kinases.
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