scholarly journals Chronic sustained and intermittent hypoxia reduce function of ATP-sensitive potassium channels in nucleus of the solitary tract

2008 ◽  
Vol 295 (5) ◽  
pp. R1555-R1562 ◽  
Author(s):  
Weirong Zhang ◽  
Flávia R. Carreño ◽  
J. Thomas Cunningham ◽  
Steve W. Mifflin
Keyword(s):  
Intermittent Hypoxia ◽  
Neuronal Excitability ◽  
Reversal Potential ◽  
Outward Current ◽  
Second Order ◽  
Neural Function ◽  
Solitary Tract ◽  
Carotid Bodies ◽  
Bath Application ◽  
Induced Changes

Activation of neuronal ATP-sensitive potassium (KATP) channels is an important mechanism that protects neurons and conserves neural function during hypoxia. We investigated hypoxia (bath gassed with 95% N2-5% CO2 vs. 95% O2-5% CO2 in control)-induced changes in KATP current in second-order neurons of peripheral chemoreceptors in the nucleus of the solitary tract (NTS). Hypoxia-induced KATP currents were compared between normoxic (Norm) rats and rats exposed to 1 wk of either chronic sustained hypoxia (CSH) or chronic intermittent hypoxia (CIH). Whole cell recordings of NTS second-order neurons identified after 4-(4-(dihexadecylamino)styryl)- N-methylpyridinium iodide (DiA) labeling of the carotid bodies were obtained in a brain stem slice. In Norm cells ( n = 9), hypoxia (3 min) induced an outward current of 12.7 ± 1.1 pA with a reversal potential of −73 ± 2 mV. This current was completely blocked by the KATP channel blocker tolbutamide (100 μM). Bath application of the KATP channel opener diazoxide (200 μM, 3 min) evoked an outward current of 21.8 ± 5.8 pA ( n = 6). Hypoxia elicited a significantly smaller outward current in both CSH (5.9 ± 1.4 pA, n = 11; P < 0.01) and CIH (6.8 ± 1.7 pA, n = 6; P < 0.05) neurons. Diazoxide elicited a significantly smaller outward current in CSH (3.9 ± 1.0 pA, n = 5; P < 0.05) and CIH (2.9 ± 0.9 pA, n = 3; P < 0.05) neurons. Western blot analysis showed reduced levels of KATP potassium channel subunits Kir6.1 and Kir6.2 in the NTS from CSH and CIH rats. These results suggest that hypoxia activates KATP channels in NTS neurons receiving monosynaptic chemoreceptor afferent inputs. Chronic exposure to either sustained or intermittent hypoxia reduces KATP channel function in NTS neurons. This may represent a neuronal adaptation that preserves neuronal excitability in crucial relay neurons in peripheral chemoreflex pathways.

Nitric Oxide Activates Leak K+ Currents in the Presumed Cholinergic Neuron of Basal Forebrain

2007 ◽  
Vol 98 (6) ◽  
pp. 3397-3410 ◽  
Author(s):  
Youngnam Kang ◽  
Yoshie Dempo ◽  
Atsuko Ohashi ◽  
Mitsuru Saito ◽  
Hiroki Toyoda ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Basal Forebrain ◽  
Reversal Potential ◽  
Soluble Guanylyl Cyclase ◽  
Outward Current ◽  
Pump Current ◽  
Atp Depletion ◽  
Equilibrium Potential ◽  
No Donor ◽  
Bath Application

Learning and memory are critically dependent on basal forebrain cholinergic (BFC) neuron excitability, which is modulated profoundly by leak K+ channels. Many neuromodulators closing leak K+ channels have been reported, whereas their endogenous opener remained unknown. We here demonstrate that nitric oxide (NO) can be the endogenous opener of leak K+ channels in the presumed BFC neurons. Bath application of 1 mM S-nitroso- N-acetylpenicillamine (SNAP), an NO donor, induced a long-lasting hyperpolarization, which was often interrupted by a transient depolarization. Soluble guanylyl cyclase inhibitors prevented SNAP from inducing hyperpolarization but allowed SNAP to cause depolarization, whereas bath application of 0.2 mM 8-bromoguanosine-3′,5′-cyclomonophosphate (8-Br-cGMP) induced a similar long-lasting hyperpolarization alone. These observations indicate that the SNAP-induced hyperpolarization and depolarization are mediated by the cGMP-dependent and -independent processes, respectively. When examined with the ramp command pulse applied at –70 mV under the voltage-clamp condition, 8-Br-cGMP application induced the outward current that reversed at K+ equilibrium potential ( EK) and displayed Goldman-Hodgkin-Katz rectification, indicating the involvement of voltage-independent K+ current. By contrast, SNAP application in the presumed BFC neurons either dialyzed with the GTP-free internal solution or in the presence of 10 μM Rp-8-bromo-β-phenyl-1,N2-ethenoguanosine 3′,5′-cyclic monophosphorothioate sodium salt, a protein kinase G (PKG) inhibitor, induced the inward current that reversed at potentials much more negative than EK and close to the reversal potential of Na+-K+ pump current. These observations strongly suggest that NO activates leak K+ channels through cGMP-PKG-dependent pathway to markedly decrease the excitability in BFC neurons, while NO simultaneously causes depolarization by the inhibition of Na+-K+ pump through ATP depletion.

scholarly journals Evidence That Histamine is a Neurotransmitter of Photoreceptors in the Locust Ocellus

1988 ◽  
Vol 138 (1) ◽  
pp. 205-219 ◽  
Author(s):  
PETER J. SIMMONS ◽  
ROGER C. HARDIE
Keyword(s):  
Biogenic Amines ◽  
Reversal Potential ◽  
Outward Current ◽  
Second Order ◽  
Dependent Manner ◽  
Tonic Component ◽  
Hyperpolarizing Response ◽  
Histamine Response ◽  
Dose Dependent ◽  
Initial Peak

The results presented here are consistent with the hypothesis that histamine is the major neurotransmitter released by photoreceptors of locust ocelli. 1. When histamine is injected by ionophoresis into the locust ocellar neuropile, large second-order neurones (L-neurones) hyperpolarize in a dose-dependent manner, and responses to light in these neurones are diminished in amplitude. Both histamine and the illumination of ocellar photoreceptors caused an outward current across the membrane. 2. Hyperpolarizing potentials in L-neurones evoked by histamine had the same reversal potential as hyperpolarizing potentials evoked by photoreceptor illumination. 3. When applied ionophoretically in the ocellus, other biogenic amines, including octopamine, dopamine and noradrenaline, had no effect on the L-neurones. Both gamma-aminobutyricacid and acetylcholine, however, depolarized L-neurones and diminished responses to light. 4. Curare blocked the L-neurone's responses to histamine and light. The histamine response recovered fully. The initial peak hyperpolarizing response to increased light recovered, but the more sustained plateau hyperpolarizing potential did not. 5. Hexamethonium bromide prolonged the response of an L-neurone to histamine, and increased the tonic component of the response to light.

Galanin Inhibits Gut-Related Vagal Neurons in Rats

2004 ◽  
Vol 91 (5) ◽  
pp. 2330-2343 ◽  
Author(s):  
Zhenjun Tan ◽  
Ronald Fogel ◽  
Chunhui Jiang ◽  
Xueguo Zhang
Keyword(s):  
Potassium Channel ◽  
Reversal Potential ◽  
Outward Current ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Solitary Tract ◽  
Membrane Hyperpolarization ◽  
Dorsal Motor Nucleus

Galanin plays an important role in the regulation of food intake, energy balance, and body weight. Many galanin-positive fibers as well as galanin-positive neurons were seen in the dorsal vagal complex, suggesting that galanin produces its effects by actions involving vagal neurons. In the present experiment, we used tract-tracing and neurophysiological techniques to evaluate the origin of the galaninergic fibers and the effect of galanin on neurons in the dorsal vagal complex. Our results reveal that the nucleus of the solitary tract is the major source of the galanin terminals in the dorsal vagal complex. In vivo experiments demonstrated that galanin inhibited the majority of gut-related neurons in the dorsal motor nucleus of the vagus. In vitro experiments demonstrated that galanin inhibited the majority of stomach-projecting neurons in the dorsal motor nucleus of the vagus by suppressing spontaneous activity and/or producing a fully reversible dose-dependent membrane hyperpolarization and outward current. The galanin-induced hyperpolarization and outward current persisted after synaptic input was blocked, suggesting that galanin acts directly on receptors of neurons in the dorsal motor nucleus of the vagus. The reversal potential induced by galanin was close to the potassium ion potentials of the Nernst equation and was prevented by the potassium channel blocker tetraethylammonium, indicating that the inhibitory effect of galanin was mediated by a potassium channel. These results indicate that the dorsal motor nucleus of the vagus is inhibited by galanin derived predominantly from neurons in the nucleus of the solitary tract projecting to the dorsal motor nucleus of the vagus nerve. Galanin is one of the neurotransmitters involved in the vago-vagal reflex.

Electrogenic Hyperpolarization-Elicited Chloride Transporter Current in Blue Cones of Zebrafish Retinal Slices

1997 ◽  
Vol 77 (3) ◽  
pp. 1447-1459 ◽  
Author(s):  
Shih-Fang Fan ◽  
Stephen Yazulla
Keyword(s):  
Time Course ◽  
Reversal Potential ◽  
Outward Current ◽  
Inhibitory Effect ◽  
Disulfonic Acid ◽  
Channel Blockers ◽  
Voltage Range ◽  
Bath Application ◽  
Cell Recording ◽  
Retinal Slices

Fan, Shih-Fang and Stephen Yazulla. Electrogenic hyperpolarization-elicited chloride transporter current in blue cones of zebrafish retinal slices. J. Neurophysiol. 77: 1447–1459, 1997. Voltage-activated currents in blue cones of the retinal slice of zebrafish were characterized using whole cell recording techniques. Depolarizing-elicited currents were recorded: an outward tetraethylammonium (TEA)-sensitive K+ current ( I Kx), an outward Ca2+-activated Cl− current ( I Cl(Ca)), from which we inferred an inward Ca2+ current ( I Ca) as well as a hyperpolarizing-elicited nonselective inward cation current ( I h). In addition, hyperpolarizing steps elicited an outward current ( I out-h) in about one-third of the blue cones. I out-h seems to be carried by inward transported Cl− because it was abolished by equimolar substitution of bath Cl− with acetate; equimolar substitution of Na+ with choline or TEA had no effect; it was not affected by Cl− channel blockers, anthracene-9-carboxylic acid, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, N-phenylanthranilic acid (DPC), niflumic acid, and 4-acetamido-4′-isothiocyanostilbene-2,2′-disulfonic acid but was suppressed by Cl− transporter blockers acetalzolamide, bumetanide, N-ethylmaleimide, furosemide, and vanadate, and no reversal potential was found. In addition, this current was suppressed by ouabains but unrelated to their Na+-K+-ATPase inhibitory effect, was not suppressed by Co2+ or nifedipine, was not affected by the gap junction decoupler, 2-octanol, was increased by bath application of Cs+, presumably due to suppression of I h, which was masked by I out-h, and was suppressed by intense light. Similar current also was found in the short cones and double cones. As I out-h operates over the same voltage range, and with similar magnitude and time course as I h, we suggest that I out-h contributes to the modulation of the photoresponse of cones.

scholarly journals Respiratory Rhythm Generation and Synaptic Inhibition of Expiratory Neurons in Pre-Bötzinger Complex: Differential Roles of Glycinergic and GABAergic Neural Transmission

1997 ◽  
Vol 77 (4) ◽  
pp. 1853-1860 ◽  
Author(s):  
Xuesi M. Shao ◽  
Jack L. Feldman
Keyword(s):  
Voltage Clamp ◽  
Respiratory Rhythm ◽  
Reversal Potential ◽  
Outward Current ◽  
Membrane Conductance ◽  
Rhythm Generation ◽  
Inspiratory Phase ◽  
Bath Application ◽  
Bötzinger Complex ◽  
Expiratory Neurons

Shao, Xuesi M. and Jack L. Feldman. Respiratory rhythm generation and synaptic inhibition of expiratory neurons in pre-Bötzinger complex: differential roles of glycinergic and GABAergic neural transmission. J. Neurophysiol. 77: 1853–1860, 1997. A key distinction between neural pacemaker and conventional network models for the generation of breathing rhythm in mammals is whether phasic reciprocal inhibitory interactions between inspiratory and expiratory neurons are required. In medullary slices from neonatal rats generating respiratory-related rhythm, we measured the phasic inhibitory inputs to expiratory neurons with the use of whole cell patch clamp in the hypothesized rhythm generation site, the pre-Bötzinger complex (pre-BötC). Expiratory neurons, which generate tonic impulse activity during the expiratory period, exhibited inhibitory postsynaptic potentials (IPSPs) synchronized to the periodic inspiratory bursts of the hypoglossal nerve root (XIIn). Bath application of the glycine receptor antagonist strychnine (STR; 5–10 μM) reversibly blocked these inspiratory-phase IPSPs, whereas the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline (BIC; 10–100 μM) had no effect on these IPSPs. Replacing the control in vitro bathing solution with a Cl−-free solution also abolished these IPSPs. Respiratory-related rhythmic activity was not abolished when inspiratory-phase IPSPs were blocked. The frequency and strength of XIIn rhythmic activity increased and seizurelike activity was produced when either STR, BIC, or Cl−-free solution was applied. Inspiratory-phase IPSPs were stable after establishment of whole cell patch conditions (patch pipettes contained 7 mM Cl−). Under voltage clamp, the reversal potential of inspiratory-phase inhibitory postsynaptic currents (IPSCs) was −75 mV. The current-voltage ( I- V) curve for IPSCs shifted to the right when extracellular Cl− concentration was reduced by 50% (70 mM) and the reversal potential was reduced to −60 mV, close to the new Cl− Nernst potential. In tetrodotoxin (0.5 μM) under voltage clamp (holding potential = −45 mV), local application of glycine (1 mM) over pre-BötC induced an outward current and an increase in membrane conductance in expiratory neurons. The effect was blocked by bath application of STR (0.8–1 μM). Local application of the GABAA receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP, 1 mM) induced an outward current and an increase in membrane conductance that was blocked by BIC (10–100 mM). Under voltage clamp (holding potential = −45 mV), we analyzed spontaneous IPSCs during expiration in expiratory neurons. Bath application of BIC (10 μM) reduced the IPSC frequency (from 2.2 to 0.3 per s), whereas the inspiratory-phase IPSCs did not change. Bath application of STR (8–10 μM) abolished both IPSCs. These results indicate that 1) reciprocal inhibition of expiratory neurons is glycinergic and mediated by a glycine-activated Cl− channel that is not required for respiratory-related rhythm generation in neonatal rat medullary slices; 2) endogenous GABA and glycine modulate the excitability of respiratory neurons and affect respiratory pattern in the slice preparation; 3) both glycine and GABAA receptors are found on pre-BötC expiratory neurons, and these receptors are sensitive to STR and BIC, respectively; 4) glycine and GABAA inhibitory mechanisms play different functional roles in expiratory neurons: both glycine and GABAA receptors modulate neuronal excitability, whereas glycinergic transmission alone is responsible for reciprocal inhibition; and 5) intracellular Cl− concentration in these neonatal expiratory neurons is similar to that in adults.

Epigenetic regulation of genes in learning and memory

2010 ◽  
Vol 48 ◽  
pp. 263-274 ◽  
Author(s):  
Tania L. Roth ◽  
Eric D. Roth ◽  
J. David Sweatt
Keyword(s):  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Epigenetic Regulation ◽  
Memory Formation ◽  
Covalent Modification ◽  
Gene Activity ◽  
Neural Function ◽  
Post Translational Modifications ◽  
Novel Approach ◽  
Induced Changes

Rapid advances in the field of epigenetics are revealing a new way to understand how we can form and store strong memories of significant events in our lives. Epigenetic modifications of chromatin, namely the post-translational modifications of nuclear proteins and covalent modification of DNA that regulate gene activity in the CNS (central nervous system), continue to be recognized for their pivotal role in synaptic plasticity and memory formation. At the same time, studies are correlating aberrant epigenetic regulation of gene activity with cognitive dysfunction prevalent in CNS disorders and disease. Epigenetic research, then, offers not only a novel approach to understanding the molecular transcriptional mechanisms underlying experience-induced changes in neural function and behaviour, but potential therapeutic treatments aimed at alleviating cognitive dysfunction. In this chapter, we discuss data regarding epigenetic marking of genes in adult learning and memory formation and impairment thereof, as well as data showcasing the promise for manipulating the epigenome in restoring memory capacity.

Neuronal Sodium Leak Channel Is Responsible for the Detection of Sodium in the Rat Median Preoptic Nucleus

2011 ◽  
Vol 105 (2) ◽  
pp. 650-660 ◽  
Author(s):  
Christina Tremblay ◽  
Emmanuelle Berret ◽  
Mélaine Henry ◽  
Benjamin Nehmé ◽  
Louis Nadeau ◽  
...  
Keyword(s):  
Close Contact ◽  
Critical Role ◽  
Reversal Potential ◽  
Outward Current ◽  
The Body ◽  
Equilibrium Potential ◽  
Preoptic Nucleus ◽  
Leak Channel ◽  
Median Preoptic Nucleus ◽  
Electrophysiological Recordings

Sodium (Na+) ions are of primary importance for hydromineral and cardiovascular homeostasis, and the level of Na+ in the body fluid compartments [plasma and cerebrospinal fluid (CSF)] is precisely monitored in the hypothalamus. Glial cells seem to play a critical role in the mechanism of Na+ detection. However, the precise role of neurons in the detection of extracellular Na+ concentration ([Na+]out) remains unclear. Here we demonstrate that neurons of the median preoptic nucleus (MnPO), a structure in close contact with the CSF, are specific Na+ sensors. Electrophysiological recordings were performed on dissociated rat MnPO neurons under isotonic [Na+] (100 mM NaCl) with local application of hypernatriuric (150, 180 mM NaCl) or hyponatriuric (50 mM NaCl) external solution. The hyper- and hyponatriuric conditions triggered an in- and an outward current, respectively. The reversal potential of the current matched the equilibrium potential of Na+, indicating that a change in [Na+]out modified the influx of Na+ in the MnPO neurons. The conductance of the Na+ current was not affected by either the membrane potential or the [Na+]out. Moreover, the channel was highly selective for lithium over guanidinium. Together, these data identified the channel as a Na+ leak channel. A high correlation between the electrophysiological recordings and immunofluorescent labeling for the NaX channel in dissociated MnPO neurons strongly supports this channel as a candidate for the Na+ leak channel responsible for the Na+-sensing ability of rat MnPO neurons. The absence of NaX labeling and of a specific current evoked by a change in [Na+]out in mouse MnPO neurons suggests species specificity in the hypothalamus structures participating in central Na+ detection.

Whole cell current analyses of pancreatic acinar AR42J cells. I. Voltage- and Ca(2+)-activated currents

1991 ◽  
Vol 260 (5) ◽  
pp. C934-C948 ◽  
Author(s):  
K. Kusano ◽  
H. Gainer
Keyword(s):  
Reversal Potential ◽  
Outward Current ◽  
Pancreatic Acinar Cells ◽  
Equilibrium Potential ◽  
Channel Blockers ◽  
Whole Cell ◽  
Inward Current ◽  
Tail Current ◽  
Ar42j Cells ◽  
Conductance Increase

Voltage- and Ca(2+)-activated whole cell currents were studied in AR42J cells, a clonal cell line derived from rat pancreatic acinar cells, using a patch electrode voltage-clamp technique. Four kinds of ionic currents were identified by their ionic dependencies, pharmacological properties, and kinetic parameters: 1) an outward current flow due mainly to a voltage-dependent K(+)-conductance increase, 2) an initial transient inward current due to an Na(+)-conductance increase, 3) transient and long-duration inward current due to a Ca(2+)-conductance increase, and 4) a slowly activating inward current that persists over the duration of the depolarizing pulse and deactivates slowly upon repolarization, producing a slow inward tail current. The slow inward tail current was particularly robust and was interpreted as due to a Ca(2+)-activated Cl(-)-conductance increase, since 1) the generation of this current was blocked by removing the extracellular Ca2+, applying Ca(2+)-channel blockers (Cd2+, nifedipine), or by lowering the intracellular Ca2+ concentration [( Ca2+]i) with EGTA; and 2) the reversal potential (Erev) of the slow inward tail current was close to 0 mV in the control condition (152 mM [Cl-]o/154 mM [Cl-]i), and changes of the [Cl-]o/[Cl )i ratio shifted the Erev toward the predicted Cl- equilibrium potential.

Changes in membrane currents of hippocampal neurons evoked by brief anoxia

1989 ◽  
Vol 62 (1) ◽  
pp. 15-30 ◽  
Author(s):  
K. Krnjevic ◽  
J. Leblond
Keyword(s):  
Hippocampal Neurons ◽  
Hippocampal Slices ◽  
Reversal Potential ◽  
Outward Current ◽  
Membrane Currents ◽  
Sprague Dawley ◽  
Persistent Currents ◽  
Inward Currents ◽  
The Difference ◽  
Conductance Increase

1. Effects of anoxia (2-4 min of 95% N2-5% CO2) on membrane currents of CA1 neurons were studied by single-electrode voltage clamp in hippocampal slices (from Sprague-Dawley rats) kept in an interface-type chamber at 33.5 degree. 2. When recording with KCl electrodes at a holding potential (VH) near-70 mV, anoxia evoked a slow outward current [0.18 +/- 0.06 (SE) nA], accompanied by a conductance increase ( + 46 +/- 20%, mean +/- SE). The difference current evoked by N2 had a reversal potential near-100 mV. It was much smaller in presence of 2-4 mM extracellular Cs, and any remaining outward current was abolished by 10 mM tetraethylammonium (TEA). Only inward currents were observed when recording with CsCl electrodes. 3. Inward relaxations evoked by large hyperpolarizing pulses from VH less than or equal to - 70 mV (Q-type) were not significantly depressed by anoxia (-1.5 +/- 6.0%). 4. Some voltage-dependent outward currents (evoked by 200-ms depolarizing pulses) were depressed during anoxia: 1) a fast-inactivating (A-like) current, obtained at VH less than or equal to -70 mV and suppressed by 200 microM 4-AP, was reduced by 25.6 +/- 7.3% (n = 5); 2) a slower, noninactivating (C-like) current, suppressed by TEA, was reduced by 52 +/- 7.2% (n = 16). Neither of these currents (1 or 2) was observed when recording with 2- to 3-M CsCl electrodes; and 3) small (M-like) inward relaxations, observed at VH approximately -40 mV 5. Net inward currents could be evoked after blockage of GK with 10 mM TEA when recording with KCl electrodes or by recording with CsCl electrodes. At VH less than or equal to -70 mV, large, transient, and incompletely controlled currents were evoked by depolarizing pulses; at VH less than or equal to -50 mV, smaller and more persistent currents were evoked by depolarizing pulses (L-like), and transient currents (T-like?) were seen immediately after hyperpolarizing pulses. 6.L-type currents (at VH less than or equal to -50 mV) were nearly abolished after 1-2 min anoxia (by approximately 90%). This was equally true of the currents evoked by constant pulses or peak currents in I-V plots. After reoxygenation, recovery was biphasic, with a quick early phase (to 50-80% in 2 min) and then a much slower one (to 60-90% by 10-15 min).(ABSTRACT TRUNCATED AT 400 WORDS)

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