Properties of amino acid neurotransmitter receptors of embryonic cortical neurons when activated by exogenous and endogenous agonists. Blanton, M G & Kriegstein, A R J Neurophysiol, 67(5):1185–1200, United States, May, 1992.
abstract   bibtex   
1. The properties of receptors for amino acid neurotransmitters expressed by developing cortical neurons were studied with the use of whole-cell recording in the intact cerebral cortex of embryonic turtles in vitro. The inhibitory agonist gamma-aminobutyric acid (GABA) and the excitatory agonist glutamate were focally applied to single cells under voltage clamp, and the ionic dependence, voltage dependence, and pharmacological sensitivity of the responses were characterized. The responses mediated by a glutamate receptor subtype, the N-methyl-D-aspartate (NMDA) receptor, produced by glutamate and by evoked release of an endogenous excitatory agonist, were compared further. Fluctuation analysis was used to characterize the properties of the NMDA channels and the mechanism of action of receptor antagonists. 2. When postmitotic neurons first appeared at stage 15, all neurons tested responded to GABA with a current that reversed at the equilibrium potential for chloride ions and that was sensitive to the GABAA receptor antagonist bicuculline methiodide (BMI). As development proceeded, an increasing proportion of neurons also responded with a BMI-insensitive current that reversed near the equilibrium potential for potassium ions. This current was blocked by the GABAB receptor antagonist 3-amino-2-propyl phosponic acid (phaclofen). The GABAB agonist baclofen, however, failed to produce a detectable postsynaptic current. 3. Neurons at stage 15 showed a biphasic response to glutamate that reversed at the equilibrium potential for cations. All neurons tested showed a slow, sustained response associated with an increase in current variance compared with background, and, as development proceeded, an increasing proportion also exhibited a fast, transient response. Both fast and slow responses varied linearly with voltage in the absence of Mg2+ ions, but the addition of Mg2+ ions to the bathing medium attenuated the slow response at hyperpolarized potentials. As a result, the current-voltage relation of the slow response in the presence of Mg2+ ions exhibited a region of negative slope conductance, like that of currents mediated by NMDA receptors. 4. The fast and slow responses to glutamate differed in their pharmacological sensitivity. The fast responses were sensitive to the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whereas the slow responses were sensitive to the NMDA receptor antagonist D(-)-2-amino-5-phosphonovalerate (D-APV). 5. When cells were held at -70 mV, glutamate evoked a fluctuating current consisting of channel currents with a mean open time, tau, of 4.42 +/- 0.47 (SE) ms in early postmitotic neurons at stage 15 and 4.99 +/- 0.38 ms at stages 17-20.(ABSTRACT TRUNCATED AT 400 WORDS)
@ARTICLE{Blanton1992-az,
  title    = "Properties of amino acid neurotransmitter receptors of embryonic
              cortical neurons when activated by exogenous and endogenous
              agonists",
  author   = "Blanton, M G and Kriegstein, A R",
  abstract = "1. The properties of receptors for amino acid neurotransmitters
              expressed by developing cortical neurons were studied with the
              use of whole-cell recording in the intact cerebral cortex of
              embryonic turtles in vitro. The inhibitory agonist
              gamma-aminobutyric acid (GABA) and the excitatory agonist
              glutamate were focally applied to single cells under voltage
              clamp, and the ionic dependence, voltage dependence, and
              pharmacological sensitivity of the responses were characterized.
              The responses mediated by a glutamate receptor subtype, the
              N-methyl-D-aspartate (NMDA) receptor, produced by glutamate and
              by evoked release of an endogenous excitatory agonist, were
              compared further. Fluctuation analysis was used to characterize
              the properties of the NMDA channels and the mechanism of action
              of receptor antagonists. 2. When postmitotic neurons first
              appeared at stage 15, all neurons tested responded to GABA with a
              current that reversed at the equilibrium potential for chloride
              ions and that was sensitive to the GABAA receptor antagonist
              bicuculline methiodide (BMI). As development proceeded, an
              increasing proportion of neurons also responded with a
              BMI-insensitive current that reversed near the equilibrium
              potential for potassium ions. This current was blocked by the
              GABAB receptor antagonist 3-amino-2-propyl phosponic acid
              (phaclofen). The GABAB agonist baclofen, however, failed to
              produce a detectable postsynaptic current. 3. Neurons at stage 15
              showed a biphasic response to glutamate that reversed at the
              equilibrium potential for cations. All neurons tested showed a
              slow, sustained response associated with an increase in current
              variance compared with background, and, as development proceeded,
              an increasing proportion also exhibited a fast, transient
              response. Both fast and slow responses varied linearly with
              voltage in the absence of Mg2+ ions, but the addition of Mg2+
              ions to the bathing medium attenuated the slow response at
              hyperpolarized potentials. As a result, the current-voltage
              relation of the slow response in the presence of Mg2+ ions
              exhibited a region of negative slope conductance, like that of
              currents mediated by NMDA receptors. 4. The fast and slow
              responses to glutamate differed in their pharmacological
              sensitivity. The fast responses were sensitive to the non-NMDA
              receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX),
              whereas the slow responses were sensitive to the NMDA receptor
              antagonist D(-)-2-amino-5-phosphonovalerate (D-APV). 5. When
              cells were held at -70 mV, glutamate evoked a fluctuating current
              consisting of channel currents with a mean open time, tau, of
              4.42 +/- 0.47 (SE) ms in early postmitotic neurons at stage 15
              and 4.99 +/- 0.38 ms at stages 17-20.(ABSTRACT TRUNCATED AT 400
              WORDS)",
  journal  = "J Neurophysiol",
  volume   =  67,
  number   =  5,
  pages    = "1185--1200",
  month    =  may,
  year     =  1992,
  address  = "United States",
  language = "en"
}

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