Volatile anesthetics gate a chloride current in postnatal rat hippocampal neurons

Abstract Background Evidence indicates that the anesthetic-sparing effects of α2-adrenergic receptor (AR) agonists involve α2A-AR heteroreceptors on nonadrenergic neurons. Since volatile anesthetics inhibit neurotransmitter release by reducing synaptic vesicle (SV) exocytosis, the authors hypothesized that α2-AR agonists inhibit nonadrenergic SV exocytosis and thereby potentiate presynaptic inhibition of exocytosis by isoflurane. Methods Quantitative imaging of fluorescent biosensors of action potential–evoked SV exocytosis (synaptophysin-pHluorin) and Ca2+ influx (GCaMP6) were used to characterize presynaptic actions of the clinically used α2-AR agonists dexmedetomidine and clonidine, and their interaction with isoflurane, in cultured rat hippocampal neurons. Results Dexmedetomidine (0.1 μM, n = 10) or clonidine (0.5 μM, n = 8) inhibited action potential–evoked exocytosis (54 ± 5% and 59 ± 8% of control, respectively; P < 0.001). Effects on exocytosis were blocked by the subtype-nonselective α2-AR antagonist atipamezole or the α2A-AR–selective antagonist BRL 44408 but not by the α2C-AR–selective antagonist JP 1302. Dexmedetomidine inhibited exocytosis and presynaptic Ca2+ influx without affecting Ca2+ coupling to exocytosis, consistent with an effect upstream of Ca2+–exocytosis coupling. Exocytosis coupled to both N-type and P/Q-type Ca2+ channels was inhibited by dexmedetomidine or clonidine. Dexmedetomidine potentiated inhibition of exocytosis by 0.7 mM isoflurane (to 42 ± 5%, compared to 63 ± 8% for isoflurane alone; P < 0.05). Conclusions Hippocampal SV exocytosis is inhibited by α2A-AR activation in proportion to reduced Ca2+ entry. These effects are additive with those of isoflurane, consistent with a role for α2A-AR presynaptic heteroreceptor inhibition of nonadrenergic synaptic transmission in the anesthetic-sparing effects of α2A-AR agonists.

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Lithium ions in nanomolar concentration modulate glycine-activated chloride current in rat hippocampal neurons

Neurochemistry International ◽

10.1016/j.neuint.2016.02.007 ◽

2016 ◽

Vol 94 ◽

pp. 67-73 ◽

Cited By ~ 2

Author(s):

E.I. Solntseva ◽

J.V. Bukanova ◽

R.V. Kondratenko ◽

V.G. Skrebitsky

Keyword(s):

Hippocampal Neurons ◽

Chloride Current ◽

Lithium Ions ◽

Nanomolar Concentration

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A714 VOLATILE ANESTHETICS GATE A NOVEL CHLORIDE CONDUCTANCE IN CULTURED POST-NATAL RAT HIPPOCAMPAL NEURONS

Anesthesiology ◽

10.1097/00000542-199009001-00712 ◽

1990 ◽

Vol 73 (3A) ◽

pp. NA-NA

Author(s):

J. Yang ◽

C. F. Zorumski

Keyword(s):

Hippocampal Neurons ◽

Volatile Anesthetics ◽

Chloride Conductance

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Antiviral drug ivermectin in nanomolar concentrations inhibits glycine-induced chloride current in rat hippocampal neurons

Bulletin of Experimental Biology and Medicine ◽

10.47056/0365-9615-2020-170-11-613-617 ◽

2020 ◽

Vol 170 (11) ◽

pp. 613-617

Author(s):

J. V. Bukanova ◽

◽

E. I. Solntseva ◽

R. V. Kondratenko ◽

V. G. Skrebitsky ◽

...

Keyword(s):

Hippocampal Neurons ◽

Antiviral Drug ◽

Chloride Current

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Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons

Journal of Neurophysiology ◽

10.1152/jn.1993.70.4.1339 ◽

1993 ◽

Vol 70 (4) ◽

pp. 1339-1349 ◽

Cited By ~ 113

Author(s):

M. V. Jones ◽

N. L. Harrison

Keyword(s):

Charge Transfer ◽

Gabaa Receptor ◽

Hippocampal Neurons ◽

Slow Component ◽

Volatile Anesthetics ◽

Fast Component ◽

Synaptic Inhibition ◽

Inhibitory Postsynaptic Currents ◽

Postsynaptic Currents ◽

Kinetics Of

1. The effects of the volatile anesthetics enflurane, halothane, and isoflurane on gamma-aminobutyric acid (GABA) receptor-mediated inhibitory postsynaptic currents (IPSCs) were studied in cultured rat hippocampal neurons. The experimental concentrations of anesthetics were measured directly using gas chromatography. All three anesthetics increased the overall duration of IPSCs, measured as the time to half-decay (T1/2). Clinically effective concentrations of anesthetics [between 0.5 and 1.5 times MAC (minimum alveolar concentration)] produced between 100 and 400% increases in T1/2. These effects were fully reversible, and did not involve alterations in the reversal potential for the IPSC (EIPSC). 2. The decay of the IPSC was fitted as a sum of two exponential functions, yielding a fast component (tau fast = 20 ms), and a slow component (tau slow = 77 ms), such that the fast component accounted for 79% of the IPSC amplitude and 52% of the total charge transfer. All three anesthetics produced concentration-related increases in the amplitude and charge transfer of the slow component, while simultaneously decreasing the amplitude and charge transfer of the fast component. Thus T1/2 approximated tau fast under control conditions, but approximated tau slow in the presence of the anesthetics. 3. Varying the calcium chelating agents in the recording pipettes had no effect on the quality or magnitude of alterations in IPSC kinetics produced by halothane, suggesting that variations in intracellular calcium levels are not required for the effect of halothane on the time course of the IPSC. 4. The (+)-stereoisomer of isoflurane produced greater increases in the duration of the IPSC than the (-)-isomer when applied at approximately equal concentrations, suggesting that there is a structurally selective site of interaction for isoflurane that modulates the GABAA receptor. 5. These results suggest that the previously shown abilities of volatile anesthetics to potentiate responses to exogenously applied GABA and to prolong the duration of GABA-mediated synaptic inhibition may be due to an alteration in the gating kinetics of the GABAA receptor/channel complex. Prolongation of synaptic inhibition in the CNS is consistent with the physiological effects that accompany anesthesia and may contribute to the mechanism of anesthetic action.

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Changes in spontaneous firing patterns of the rat hippocampal neurons by volatile anesthetics

Neuroscience Research Supplements ◽

10.1016/0921-8696(87)90180-0 ◽

1987 ◽

Vol 5 ◽

pp. S82

Author(s):

Hideho Higashi ◽

Megumu Yoshimura ◽

Syunsuke Sugita ◽

Syogoro Nishi ◽

Naoshi Fujiwara ◽

...

Keyword(s):

Hippocampal Neurons ◽

Volatile Anesthetics ◽

Spontaneous Firing ◽

Firing Patterns

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Volatile Anesthetics Increase Intracellular Calcium in Cerebrocortical and Hippocampal Neurons

Anesthesiology ◽

10.1097/00000542-199904000-00029 ◽

1999 ◽

Vol 90 (4) ◽

pp. 1137-1145 ◽

Cited By ~ 45

Author(s):

Christoph H. Kindler ◽

Helge Eilers ◽

Paul Donohoe ◽

Surhan Ozer ◽

Philip E. Bickler

Keyword(s):

Intracellular Calcium ◽

Hippocampal Neurons ◽

Hippocampal Slices ◽

Brain Slices ◽

Volatile Anesthetic ◽

Volatile Anesthetics ◽

Channel Blockers ◽

Dependent Manner ◽

Free Medium ◽

Ca1 Neurons

Background An increase in intracellular calcium concentration ([Ca2+]i) in neurons has been proposed as an important effect of volatile anesthetics, because they alter signaling pathways that influence neurotransmission. However, the existing data for anesthetic-induced increases in [Ca2+]i conflict. Methods Changes in [Ca2+]i were measured using fura-2 fluorescence spectroscopy in rat cortical brain slices at 90, 185, 370, and 705 microM isoflurane. To define the causes of an increase in [Ca2+]i, slices were studied in Ca2+-free medium, in the presence of Ca2+-channel blockers, and in the presence of the Ca2+-release inhibitor azumolene. The authors compared the effect of the volatile anesthetic with that of the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane. Single-dose experiments in CA1 neurons in hippocampal slices with halothane (360 microM) and in acutely dissociated CA1 neurons with halothane (360 microM) and isoflurane (445 microM) also were performed. Results Isoflurane at 0.5, 1, and 2 minimum alveolar concentrations increased basal [Ca2+]i in cortical slices in a dose-dependent manner (P < 0.05). This increase was not altered by Ca2+-channel blockers or Ca2+-free medium but was reduced 85% by azumolene. The nonanesthetic 1,2-dichlorohexafluorocyclobutane did not increase [Ca2+]i. In dissociated CA1 neurons, isoflurane reversibly increased basal [Ca2+]i by 15 nM (P < 0.05). Halothane increased [Ca2+]i in dissociated CA1 neurons and CA1 neurons in hippocampal slices by approximately 30 nM (P < 0.05). Conclusions (1) Isoflurane and halothane reversibly increase [Ca2+]i in isolated neurons and in neurons within brain slices. (2) The increase in [Ca2+]i is caused primarily by release from intracellular stores. (3) Increases in [Ca2+]i occur with anesthetics but not with the nonanesthetic 1,2-dichlorohexafluorocyclobutane.

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