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Lysophosphatidic Acid Stimulates Neurotransmitter-Like Conductance Changes that Precede GABA and l-Glutamate in Early, Presumptive Cortical Neuroblasts
Journal article   Open access   Peer reviewed

Lysophosphatidic Acid Stimulates Neurotransmitter-Like Conductance Changes that Precede GABA and l-Glutamate in Early, Presumptive Cortical Neuroblasts

Adrienne E Dubin, Tristram Bahnson, Joshua A Weiner, Nobuyuki Fukushima and Jerold Chun
The Journal of neuroscience, Vol.19(4), pp.1371-1381
02/15/1999
DOI: 10.1523/JNEUROSCI.19-04-01371.1999
PMCID: PMC6786022
PMID: 9952414
url
https://doi.org/10.1523/JNEUROSCI.19-04-01371.1999View
Published (Version of record) Open Access

Abstract

During neurogenesis in the embryonic cerebral cortex, the classical neurotransmitters GABA and l -glutamate stimulate ionic conductance changes in ventricular zone (VZ) neuroblasts. Lysophosphatidic acid (LPA) is a bioactive phospholipid producing myriad effects on cells including alterations in membrane conductances (for review, see Moolenaar et al., 1995 ). Developmental expression patterns of its first cloned receptor gene, lp A1 /vzg-1 ( Hecht et al., 1996 ; Fukushima et al., 1998 ) in the VZ suggested that functional LPA receptors were synthesized at these early times, and thus, LPA could be an earlier stimulus to VZ cells than the neurotransmitters GABA and l -glutamate. To address this possibility, primary cultures of electrically coupled, presumptive cortical neuroblast clusters were identified by age, morphology, electrophysiological profile, BrdU incorporation, and nestin immunostaining. Single cells from cortical neuroblast cell lines were also examined. Whole-cell variation of the patch-clamp technique was used to record from nestin-immunoreactive cells after stimulation by local administration of ligands. After initial plating at embryonic day 11 (E11), cells responded only to LPA but not to GABA or l -glutamate. Continued growth in culture for up to 12 hr produced more LPA-responsive cells, but also a growing population of GABA- or l -glutamate-responsive cells. Cultures from E12 embryos showed LPA as well as GABA and l -glutamate responses, with LPA-responsive cells still representing a majority. Overall, >50% of cells responded to LPA with depolarization mediated by either chloride or nonselective cation conductances. These data implicate LPA as the earliest reported extracellular stimulus of ionic conductance changes for cortical neuroblasts and provide evidence for LPA as a novel, physiological component in CNS development.
cerebral cortex lysophosphatidic acid lysophospholipids embryonic development chloride currents cation currents LPA programmed cell death

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