Excitatory effects of GABA on procerebrum neurons in a slug

2012 ◽  
Vol 108 (4) ◽  
pp. 989-998 ◽  
Author(s):  
Suguru Kobayashi ◽  
Ryota Matsuo ◽  
Hisayo Sadamoto ◽  
Satoshi Watanabe ◽  
Etsuro Ito
Keyword(s):  
Direct Effect ◽  
Gaba Receptors ◽  
Aminobutyric Acid ◽  
Cultured Neurons ◽  
Inhibitory Postsynaptic Currents ◽  
Receptor Mrna ◽  
Postsynaptic Currents ◽  
Outward Currents ◽  
Inhibitory Transmitter ◽  
Induced Currents

Classical neurotransmitters, such as glutamate and γ-aminobutyric acid (GABA), often have different actions on invertebrate neurons from those reported for vertebrate neurons. In the terrestrial mollusk Limax, glutamate was found to function as an inhibitory transmitter in the procerebrum (PC), but it has not yet been clarified how GABA acts in the PC. We thus examined what effects GABA exerts on PC neurons in the present study. For this purpose, we first applied GABA to isolated PC preparations and recorded postsynaptic currents and potentials in PC neurons. The GABA application reduced the amplitude of inhibitory postsynaptic currents and depolarization-induced outward currents recorded in nonbursting neurons and increased the number of spontaneous spikes of nonbursting neurons. However, direct GABA-induced currents were not observed in either bursting or nonbursting neurons. These results suggest a potential direct effect of GABA on outward currents resulting in enhanced excitability of PC neurons. Next, we measured the change in [Ca2+]i in cultured PC neurons by application of GABA. The GABA application increased spontaneous Ca2+ events in cultured neurons. These Ca2+ events were ascribable to the influx of extracellular Ca2+. We then confirmed the presence of GABA and GABA receptors in the PC. The GABA-like immunoreactivity was observed in the neuropil layers of the PC, and the mRNAs for both GABAA and GABAB receptors were expressed in the PC. In particular, GABAB receptor mRNA, rather than GABAA, was found to be more abundantly expressed in the PC. These results suggest that GABA functions as an excitatory modulator for PC neurons via mainly GABAB receptors.

Modulation of γ-Aminobutyric Acid Type A Receptor–mediated Spontaneous Inhibitory Postsynaptic Currents in Auditory Cortex by Midazolam and Isoflurane

2005 ◽  
Vol 102 (5) ◽  
pp. 962-969 ◽  
Author(s):  
Yakov I. Verbny ◽  
Elliott B. Merriam ◽  
Matthew I. Banks
Keyword(s):  
Auditory Cortex ◽  
Pyramidal Cells ◽  
Type A ◽  
Aminobutyric Acid ◽  
Gaba A ◽  
Cellular Targets ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Acid Type

Background Anesthetic agents that target gamma-aminobutyric acid type A (GABA(A)) receptors modulate cortical auditory evoked responses in vivo, but the cellular targets involved are unidentified. Also, for agents with multiple protein targets, the relative contribution of modulation of GABA(A) receptors to effects on cortical physiology is unclear. The authors compared effects of the GABA(A) receptor-specific drug midazolam with the volatile anesthetic isoflurane on spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal cells of auditory cortex. Methods Whole cell recordings were obtained in murine brain slices at 34 degrees C. GABA(A) sIPSCs were isolated by blocking ionotropic glutamate receptors. Effects of midazolam and isoflurane on time course, amplitude, and frequency of sIPSCs were measured. Results The authors detected no effect of midazolam at 0.01 microM on sIPSCs, whereas midazolam at 0.1 and 1 microM prolonged the decay of sIPSCs by approximately 25 and 70%, respectively. Isoflurane at 0.1, 0.25, and 0.5 mm prolonged sIPSCs by approximately 45, 150, and 240%, respectively. No drug-specific effects were observed on rise time or frequency of sIPSCs. Isoflurane at 0.5 mm caused a significant decrease in sIPSC amplitude. Conclusions The dose dependence of isoflurane effects on GABA(A) sIPSCs in pyramidal cells is consistent with effects on auditory evoked response in vivo. By contrast, comparable effects of midazolam on GABA(A) sIPSCs arise at concentrations exceeding those currently thought to be achieved in vivo, suggesting that the cellular targets of midazolam reside elsewhere in the thalamocortical circuit or that the concentration of midazolam reached in the brain is higher than currently believed.

Propofol Modulates γ-Aminobutyric Acid–mediated Inhibitory Neurotransmission to Cardiac Vagal Neurons in the Nucleus Ambiguus

2004 ◽  
Vol 100 (5) ◽  
pp. 1198-1205 ◽  
Author(s):  
Xin Wang ◽  
Zheng-Gui Huang ◽  
Allison Gold ◽  
Evguenia Bouairi ◽  
Cory Evans ◽  
...  
Keyword(s):  
Heart Rate ◽  
Decay Time ◽  
Nucleus Ambiguus ◽  
Aminobutyric Acid ◽  
Gabaergic Neurotransmission ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Inhibitory Neurotransmission ◽  
Parasympathetic Neurons ◽  
Glycinergic Neurotransmission

Background Although it is well recognized that anesthetics modulate the central control of cardiorespiratory homeostasis, the cellular mechanisms by which anesthetics alter cardiac parasympathetic activity are poorly understood. One common site of action of anesthetics is inhibitory neurotransmission. This study investigates the effect of propofol on gamma-aminobutyric acid-mediated (GABAergic) and glycinergic neurotransmission to cardiac parasympathetic neurons. Methods Cardiac parasympathetic neurons were identified in vitro by the presence of a retrograde fluorescent tracer, and spontaneous GABAergic and glycinergic synaptic currents were examined using whole cell patch clamp techniques. Results Propofol at concentrations of 1.0 microm and greater significantly (P < 0.05) increased the duration and decay time of spontaneous GABAergic inhibitory postsynaptic currents. To determine whether the action of propofol was at presynaptic or postsynaptic sites, tetrodotoxin was applied to isolate miniature inhibitory postsynaptic currents. Propofol at concentrations of 1.0 microm and greater significantly (P < 0.05) prolonged the decay time and duration of miniature inhibitory postsynaptic currents, indicating that propofol directly alters GABAergic neurotransmission at a postsynaptic site. Propofol at high concentrations (> or =50 microm) also inhibited the frequency of both GABAergic inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents. Propofol at concentrations up to 50 microm had no effect on glycinergic neurotransmission. Conclusions Propofol may vary heart rate by modulating GABAergic neurotransmission to cardiac parasympathetic neurons. At clinically relevant concentrations (> or =1.0 microm), propofol facilitated GABAergic responses in cardiac vagal neurons by increasing decay time, which would increase inhibition of cardioinhibitory cardiac vagal neurons and evoke an increase in heart rate. At higher supraclinical concentrations (> or =50 microm), propofol inhibits GABAergic neurotransmission to cardiac vagal neurons, which would evoke a decrease in heart rate.

Effect of Isoflurane and Other Potent Inhaled Anesthetics on Minimum Alveolar Concentration, Learning, and the Righting Reflex in Mice Engineered to Express α1γ-Aminobutyric Acid Type A Receptors Unresponsive to Isoflurane

2007 ◽  
Vol 106 (1) ◽  
pp. 107-113 ◽  
Author(s):  
James M. Sonner ◽  
David F. Werner ◽  
Frank P. Elsen ◽  
Yilei Xing ◽  
Mark Liao ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Minimum Alveolar Concentration ◽  
Hippocampal Slices ◽  
Type A ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Wild Type ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Acid Type

Background Enhancement of the function of gamma-aminobutyric acid type A receptors containing the alpha1 subunit may underlie a portion of inhaled anesthetic action. To test this, the authors created gene knock-in mice harboring mutations that render the receptors insensitive to isoflurane while preserving sensitivity to halothane. Methods The authors recorded miniature inhibitory synaptic currents in hippocampal neurons from hippocampal slices from knock-in and wild-type mice. They also determined the minimum alveolar concentration (MAC), and the concentration at which 50% of animals lost their righting reflexes and which suppressed pavlovian fear conditioning to tone and context in both genotypes. Results Miniature inhibitory postsynaptic currents decayed more rapidly in interneurons and CA1 pyramidal cells from the knock-in mice compared with wild-type animals. Isoflurane (0.5-1 MAC) prolonged the decay phase of miniature inhibitory postsynaptic currents in neurons of the wild-type mice, but this effect was significantly reduced in neurons from knock-in mice. Halothane (1 MAC) slowed the decay of miniature inhibitory postsynaptic current in both genotypes. The homozygous knock-in mice were more resistant than wild-type controls to loss of righting reflexes induced by isoflurane and enflurane, but not to halothane. The MAC for isoflurane, desflurane, and halothane did not differ between knock-in and wild-type mice. The knock-in mice and wild-type mice did not differ in their sensitivity to isoflurane for fear conditioning. Conclusions gamma-Aminobutyric acid type A receptors containing the alpha1 subunit participate in the inhibition of the righting reflexes by isoflurane and enflurane. They are not, however, involved in the amnestic effect of isoflurane or immobilizing actions of inhaled agents.

Inhibitory postsynaptic currents and the effects of GABA on visually identified sacral parasympathetic preganglionic neurons in neonatal rats

1994 ◽  
Vol 72 (6) ◽  
pp. 2903-2910 ◽  
Author(s):  
I. Araki
Keyword(s):  
Receptor Antagonist ◽  
Gabab Receptor ◽  
Reversal Potential ◽  
Equilibrium Potential ◽  
Patch Clamp Technique ◽  
Whole Cell ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Gabaa Receptor Antagonist ◽  
Induced Currents

1. The actions of gamma-aminobutyric acid (GABA) on sacral parasympathetic preganglionic (SPP) neurons were examined in slice preparations using the whole cell patch-clamp technique. 2. Inhibitory postsynaptic currents (IPSCs), which were evoked by focal electrical stimulation, were recorded from SPP neurons in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a glutamate receptor antagonist. The IPSCs were substantially reduced by strychnine (1 microM), a glycine receptor antagonist. The remaining IPSCs were completely blocked by bicuculline (20 microM), a GABAA receptor antagonist. The mean peak amplitude of bicuculline-sensitive, GABAergic currents recorded at -60 mV was 53.6 +/- 10.9%, mean +/- SD (n = 8), of that of the total IPSCs. The GABAergic currents were reversed in polarity at about -30 mV, near the Cl- equilibrium potential. 3. GABA (5-50 microM) induced inward currents in SPP neurons with symmetrical internal and external Cl- concentrations. This response was completely blocked by 100 microM bicuculline. Muscimol (2-8 microM), a GABAA agonist, mimicked the GABA-induced responses, whereas a GABAB receptor agonist, baclofen (20-200 microM), produced responses in only a few cells. The GABA-induced currents reversed their polarity at approximately 0 mV, near the Cl- equilibrium potential. When the internal Cl- concentration was reduced, the reversal potential was shifted according to the Nernst equation for Cl-. 4. GABA-induced currents exhibited an outward "hump" between -35 and 15 mV. This voltage range coincided with that at which a depolarization-induced inward whole cell current was elicited.(ABSTRACT TRUNCATED AT 250 WORDS)

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