Sodium channels, GABAA receptors, and glutamate receptors develop sequentially on embryonic rat spinal cord cells

Walton, M.K.; Schaffner, AE; Barker, J. L.

doi:10.1523/jneurosci.13-05-02068.1993

Cited by 90 publications

(72 citation statements)

References 60 publications

(72 reference statements)

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“…This is consistent with experiments near the beginning of hypothalamic neurogenesis (E1.5) when all cells tested with patch-clamp recording showed a large response to GABA, but only some showed a response to glutamate (van den Pal et al, 1995). Studies in the spinal cord showed that GABA receptors are expressed in early embryogenesis and may be found even earlier than glutamate receptors (Walton et al, 1993). GABA and its synthetic enzyme are found in E6 neurons in the chick retina (De Mello et al, 1976;Frederick, 1987); this is prior to significant synaptogenesis described at El4 (Sheffield and Fischman, 1970).…”

Section: Developmentalsupporting

confidence: 89%

GABA neurotransmission in the hypothalamus: developmental reversal from Ca2+ elevating to depressing

1995

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GABA is the primary inhibitory transmitter of the adult hypothalamus, synthesized by many neurons and found in 50% of the presynaptic boutons. GABA causes a decrease in Ca2+ in mature hypothalamic neurons in vitro by depressing cellular activity through opening Cl- channels. Despite the early expression of GABAA receptors in the embryonic hypothalamus (E15), the cellular function of GABA in the developing hypothalamus has received little attention. In the present study the role of GABA in modulating intracellular Ca2+ in developing hypothalamic neurons was studied with fura-2 digital imaging. GABA (0.5- 500 microM) applied to embryonic hypothalamic neurons elicited a dramatic and rapid increase in intracellular Ca2+ This Ca2+ rise could be completely blocked by the GABAA antagonist bicuculline (20 microM) and persisted in the presence of tetrodotoxin (1 microM). The Ca2+ elevation induced by GABA was greater than that of equimolar concentrations of the excitatory transmitter glutamate in early development. The number of E15 neurons that responded to GABA with a Ca2+ rise increased during the first few days of culture, reaching 78% after 4 d in vitro. The Ca2+ rise was 87% blocked by cadmium (100 microM) and 85% blocked by nimodipine (1 microM), indicating that the mechanism of Ca2+ increase was primarily via L-type voltage operated Ca2+ channels. Addition of bicuculline to synaptically coupled cultures caused a significant decrease in Ca2+ 4–10 d after culturing, indicating hypothalamic neurons were secreting GABA at an early age of development, and that sufficient GABA was released to elicit an increase in Ca2+. This effect was seen even after blocking all glutamatergic activity with glutamate receptor antagonists. In contrast, GABA elicited no Ca2+ rise in older neurons (> 18 d in vitro), and the action of bicuculline reversed and caused a large increase in Ca2+ in spontaneously active neurons. Similar findings were obtained in cultures enriched in GABAergic neurons from the suprachiasmatic nucleus. To determine if the Ca2+ stimulating role of GABA on developing neurons was restricted to the hypothalamus and a few other regions, or whether it might exist throughout the brain, we examined the Ca2+ responses in cultured olfactory bulb, cortex, medulla, striatum, thalamus, hippocampus, and colliculus. The majority (75%) of developing neurons from each region showed a Ca2+ rise in response to GABA. Together these data suggest that GABA elevates Ca2+ in developing, but not mature, neurons from the hypothalamus and all other brain regions examined.

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Section: Developmentalsupporting

confidence: 89%

GABA neurotransmission in the hypothalamus: developmental reversal from Ca2+ elevating to depressing

1995

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“…Neurons express functional GABA receptors very early in development (Fiszman et al, 1990;Walton et al, 1993;Chen et al, 1995). Some embryonic, but not mature, neurons show Ca 2ϩ rises in response to GABA (Reichling et al, 1994;Ben-Ari et al, 1989;Yuste and Katz, 1991;Obrietan and van den Pol, 1995a).…”

Section: Discussionmentioning

confidence: 99%

Excitatory Actions of GABA after Neuronal Trauma

1996

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GABA is the dominant inhibitory neurotransmitter in the CNS. By opening Cl Ϫ channels, GABA generally hyperpolarizes the membrane potential, decreases neuronal activity, and reduces intracellular Ca 2ϩ of mature neurons. In the present experiment, we show that after neuronal trauma, GABA, both synaptically released and exogenously applied, exerted a novel and opposite effect, depolarizing neurons and increasing intracellular Ca 2ϩ . Different types of trauma that were effective included neurite transection, replating, osmotic imbalance, and excess heat. The depolarizing actions of GABA after trauma increased Ca 2ϩ levels up to fourfold in some neurons, occurred in more than half of the severely injured neurons, and was long lasting (Ͼ1 week). The mechanism for the reversed action of GABA appears to be a depolarized Cl Ϫ reversal potential that results in outward rather than inward movement of Cl Ϫ , as revealed by gramicidin-perforated whole-cell patch-clamp recording. The consequent depolarization and resultant activation of the nimodipine sensitive L-and conotoxin-sensitive N-type voltage-activated Ca 2ϩ channel allows extracellular Ca 2ϩ to enter the neuron. The long-lasting capacity to raise Ca 2ϩ may give GABA a greater role during recovery from trauma in modulating gene expression, and directing and enhancing outgrowth of regenerating neurites. On the negative side, by its depolarizing actions, GABA could increase neuronal damage by raising cytosolic Ca 2ϩ levels in injured cells. Furthermore, the excitatory actions of GABA after neuronal injury may contribute to maladaptive signal transmission in affected GABAergic brain circuits.

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“…Integrated FL from pixels within each AOI were summed and FL of equivalent background areas subtracted before conversion to log(FL). The data acquisition process and software were developed in house by Walton et al (Walton et al, 1993) and further refined by the authors for the present application.…”

Section: Voltage Probe Recording and Data Analysismentioning

confidence: 99%

Transporter-mediated GABA responses in horizontal and bipolar cells of zebrafish retina

2008

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GABA-mediated interactions between horizontal cells (HCs) and bipolar cells (BCs) transform signals within the image-processing circuitry of distal retina. To further understand this process we have studied the GABA-driven membrane responses from isolated retinal neurons. Papaindissociated retinal cells from adult zebrafish were exposed to GABAergic ligands while transmembrane potentials were monitored with a fluorescent voltage-sensitive dye (oxonol, DiBaC 4 (5)). In HCs hyperpolarizing, ionotropic GABA responses were almost never seen, nor were responses to baclofen or glycine. A GABA-induced depolarization followed by after hyperpolarization (dep/AHP) occurred in 38% of HCs. The median fluorescence increase (dep component) was 0.17 log units, about 22 mV. HC dep/AHP was not blocked by bicuculline or picrotoxin. Muscimol rarely evoked dep/AHP responses. In BCs picrotoxin sensitive, hyperpolarizing, ionotropic GABA and muscimol responses occurred in most cells. A picrotoxin insensitive dep/AHP response was seen in about 5% of BCs. The median fluorescence increase (dep component) was 0.18 log units, about 23 mV. Some BCs expressed both muscimol-induced hyperpolarizations and GABA-induced dep/AHP responses. For all cells the pooled Hill fit to median dep amplitudes, in response to treatments with a GABA concentration series, gave an apparent k of 0.61 μM and an n of 1.1. The dep/AHP responses of all cells required both extracellular Na + and Cl − , as dep/AHP was blocked reversibly by Li + substituted for Na + and irreversibly by isethionate substituted for Cl − . All cells with dep/AHP responses in zebrafish have the membrane physiology of neurons expressing GABA transporters. These cells likely accumulate GABA, a characteristic of GABAergic neurons. We suggest Na + drives GABA into these cells, depolarizing the plasma membrane and triggering Na + , K + -dependent ATPase. The ATPase activity generates AHP. In addition to a GABA clearance function, these large-amplitude transporter responses may provide an outer plexiform layer GABA sensor mechanism.

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Sodium channels, GABAA receptors, and glutamate receptors develop sequentially on embryonic rat spinal cord cells

Cited by 90 publications

References 60 publications

GABA neurotransmission in the hypothalamus: developmental reversal from Ca2+ elevating to depressing

GABA neurotransmission in the hypothalamus: developmental reversal from Ca2+ elevating to depressing

Excitatory Actions of GABA after Neuronal Trauma

Transporter-mediated GABA responses in horizontal and bipolar cells of zebrafish retina

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