QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Wu, R.-L. Articles by Barish, M. E. Search for Related Content PubMed PubMed Citation Articles by Wu, R.-L. Articles by Barish, M. E.

 Previous Article  |  Next Article 

The Journal of Neuroscience, August 15, 1998, 18(16):6261-6278

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

Rui-Lin Wu, Donna M. Butler, and Michael E. Barish

Division of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, California 91010

Hippocampal pyramidal neurons express three major voltage-dependent potassium currents, I_A, I_D, and I_K. During hippocampal development, I_A, the rapidly activating and inactivating transient potassium current, is detected soon after pyramidal neurons can be morphologically identified. Appearance of I_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_A ().

We have examined intracellular signaling pathways that could contribute to the regulation of I_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_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_A). In contrast, exposure to ML-9 or KN-62, inhibitors of myosin light chain kinase or Ca²⁺-calmodulin-dependent protein kinase II (CaMKII), reduced membrane area and I_A amplitude but did not affect I_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.

Key words: hippocampus; development; excitability; potassium channels; I_A; I_D; I_K; membrane expansion; neurite outgrowth; phosphatidylinositol 3-kinase; calcium-calmodulin-dependent protein kinase II; myosin light chain kinase

---

Copyright © 1998 Society for Neuroscience  0270-6474/98/18166261-18$05.00/0

This article has been cited by other articles:

				T. A. Roepke, A. Malyala, M. A. Bosch, M. J. Kelly, and O. K. Ronnekleiv Estrogen Regulation of Genes Important for K+ Channel Signaling in the Arcuate Nucleus Endocrinology, October 1, 2007; 148(10): 4937 - 4951. [Abstract] [Full Text] [PDF]

				A. W. Varga, L.-L. Yuan, A. E. Anderson, L. A. Schrader, G.-Y. Wu, J. R. Gatchel, D. Johnston, and J. D. Sweatt Calcium-Calmodulin-Dependent Kinase II Modulates Kv4.2 Channel Expression and Upregulates Neuronal A-Type Potassium Currents J. Neurosci., April 7, 2004; 24(14): 3643 - 3654. [Abstract] [Full Text] [PDF]

				S. Hattori, F. Murakami, and W.-J. Song Quantitative Relationship Between Kv4.2 mRNA and A-Type K+ Current in Rat Striatal Cholinergic Interneurons During Development J Neurophysiol, July 1, 2003; 90(1): 175 - 183. [Abstract] [Full Text] [PDF]

				P. Opazo, A. M. Watabe, S. G. N. Grant, and T. J. O'Dell Phosphatidylinositol 3-Kinase Regulates the Induction of Long-Term Potentiation through Extracellular Signal-Related Kinase-Independent Mechanisms J. Neurosci., May 1, 2003; 23(9): 3679 - 3688. [Abstract] [Full Text] [PDF]

				A. Czarnecki, L. Dufy-Barbe, S. Huet, M.-F. Odessa, and L. Bresson-Bepoldin Potassium channel expression level is dependent on the proliferation state in the GH3 pituitary cell line Am J Physiol Cell Physiol, April 1, 2003; 284(4): C1054 - C1064. [Abstract] [Full Text] [PDF]

				D. V Vasilyev and M. E Barish Regulation of an inactivating potassium current (IA) by the extracellular matrix protein vitronectin in embryonic mouse hippocampal neurones J. Physiol., March 15, 2003; 547(3): 859 - 871. [Abstract] [Full Text] [PDF]

				M. Martin-Caraballo and S. E. Dryer Glial Cell Line-Derived Neurotrophic Factor and Target-Dependent Regulation of Large-Conductance KCa Channels in Developing Chick Lumbar Motoneurons J. Neurosci., December 1, 2002; 22(23): 10201 - 10208. [Abstract] [Full Text] [PDF]

				L. Lhuillier and S. E. Dryer Developmental Regulation of Neuronal KCa Channels by TGFbeta 1: An Essential Role for PI3 Kinase Signaling and Membrane Insertion J Neurophysiol, August 1, 2002; 88(2): 954 - 964. [Abstract] [Full Text] [PDF]

				N. Alessandri-Haber, G. Alcaraz, C. Deleuze, F. Jullien, C. Manrique, F. Couraud, M. Crest, and P. Giraud Molecular determinants of emerging excitability in rat embryonic motoneurons J. Physiol., May 15, 2002; 541(1): 25 - 39. [Abstract] [Full Text] [PDF]

				D. J. Baro, A. Ayali, L. French, N. L. Scholz, J. Labenia, C. C. Lanning, K. Graubard, and R. M. Harris-Warrick Molecular Underpinnings of Motor Pattern Generation: Differential Targeting of Shal and Shaker in the Pyloric Motor System J. Neurosci., September 1, 2000; 20(17): 6619 - 6630. [Abstract] [Full Text] [PDF]

				T. G. Paunescu, B. L. Blazer-Yost, C. J. Vlahos, and S. I. Helman LY-294002-inhibitable PI 3-kinase and regulation of baseline rates of Na+ transport in A6 epithelia Am J Physiol Cell Physiol, July 1, 2000; 279(1): C236 - C247. [Abstract] [Full Text] [PDF]

				R.-L. Wu and M. E. Barish Modulation of a Slowly Inactivating Potassium Current, ID, by Metabotropic Glutamate Receptor Activation in Cultured Hippocampal Pyramidal Neurons J. Neurosci., August 15, 1999; 19(16): 6825 - 6837. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help