Firing Properties of GABAergic Versus Non-GABAergic Vestibular Nucleus Neurons Conferred by a Differential Balance of Potassium Currents

2007 ◽  
Vol 97 (6) ◽  
pp. 3986-3996 ◽  
Author(s):  
Aryn H. Gittis ◽  
Sascha du Lac
Keyword(s):  
Vestibular Nucleus ◽  
Brain Slices ◽  
Ionic Currents ◽  
Vestibular Nuclei ◽  
Cell Types ◽  
Delayed Rectifier ◽  
Charge Densities ◽  
Outward Currents ◽  
Firing Properties ◽  
Kinetics Of

Neural circuits are composed of diverse cell types, the firing properties of which reflect their intrinsic ionic currents. GABAergic and non-GABAergic neurons in the medial vestibular nuclei, identified in GIN and YFP-16 lines of transgenic mice, respectively, exhibit different firing properties in brain slices. The intrinsic ionic currents of these cell types were investigated in acutely dissociated neurons from 3- to 4-wk-old mice, where differences in spontaneous firing and action potential parameters observed in slice preparations are preserved. Both GIN and YFP-16 neurons express a combination of four major outward currents: Ca2+-dependent K+ currents ( IKCa), 1 mM TEA-sensitive delayed rectifier K+ currents ( I1TEA), 10 mM TEA-sensitive delayed rectifier K+ currents ( I10TEA), and A-type K+ currents ( IA). The balance of these currents varied across cells, with GIN neurons tending to express proportionately more IKCa and IA, and YFP-16 neurons tending to express proportionately more I1TEA and I10TEA. Correlations in charge densities suggested that several currents were coregulated. Variations in the kinetics and density of I1TEA could account for differences in repolarization rates observed both within and between cell types. These data indicate that diversity in the firing properties of GABAergic and non-GABAergic vestibular nucleus neurons arises from graded differences in the balance and kinetics of ionic currents.

scholarly journals Mechanisms of Sustained High Firing Rates in Two Classes of Vestibular Nucleus Neurons: Differential Contributions of Resurgent Na, Kv3, and BK Currents

2010 ◽  
Vol 104 (3) ◽  
pp. 1625-1634 ◽  
Author(s):  
Aryn H. Gittis ◽  
Setareh H. Moghadam ◽  
Sascha du Lac
Keyword(s):  
Action Potential ◽  
Vestibular Nucleus ◽  
Ionic Currents ◽  
Na Channel ◽  
Firing Rates ◽  
Neuronal Populations ◽  
Firing Range ◽  
Na Currents ◽  
The Difference ◽  
Firing Properties

To fire at high rates, neurons express ionic currents that work together to minimize refractory periods by ensuring that sodium channels are available for activation shortly after each action potential. Vestibular nucleus neurons operate around high baseline firing rates and encode information with bidirectional modulation of firing rates up to several hundred Hz. To determine the mechanisms that enable these neurons to sustain firing at high rates, ionic currents were measured during firing by using the action potential clamp technique in vestibular nucleus neurons acutely dissociated from transgenic mice. Although neurons from the YFP-16 line fire at rates higher than those from the GIN line, both classes of neurons express Kv3 and BK currents as well as both transient and resurgent Na currents. In the fastest firing neurons, Kv3 currents dominated repolarization at all firing rates and minimized Na channel inactivation by rapidly transitioning Na channels from the open to the closed state. In slower firing neurons, BK currents dominated repolarization at the highest firing rates and sodium channel availability was protected by a resurgent blocking mechanism. Quantitative differences in Kv3 current density across neurons and qualitative differences in immunohistochemically detected expression of Kv3 subunits could account for the difference in firing range within and across cell classes. These results demonstrate how divergent firing properties of two neuronal populations arise through the interplay of at least three ionic currents.

Transmural action potential and ionic current remodeling in ventricles of failing canine hearts

2002 ◽  
Vol 283 (3) ◽  
pp. H1031-H1041 ◽  
Author(s):  
Gui-Rong Li ◽  
Chu-Pak Lau ◽  
Anique Ducharme ◽  
Jean-Claude Tardif ◽  
Stanley Nattel
Keyword(s):  
Left Ventricle ◽  
Action Potential ◽  
Action Potentials ◽  
Slow Component ◽  
Ionic Current ◽  
Ionic Currents ◽  
Cell Types ◽  
Delayed Rectifier ◽  
Cardiac Repolarization ◽  
Early Afterdepolarizations

Heart failure (HF) produces important alterations in currents underlying cardiac repolarization, but the transmural distribution of such changes is unknown. We therefore recorded action potentials and ionic currents in cells isolated from the endocardium, midmyocardium, and epicardium of the left ventricle from dogs with and without tachypacing-induced HF. HF greatly increased action potential duration (APD) but attenuated APD heterogeneity in the three regions. Early afterdepolarizations (EADs) were observed in all cell types of failing hearts but not in controls. Inward rectifier K+ current ( I K1) was homogeneously reduced by ∼41% (at −60 mV) in the three cell types. Transient outward K+ current ( I to1) was decreased by 43–45% at +30 mV, and the slow component of the delayed rectifier K+ current ( I Ks) was significantly downregulated by 57%, 49%, and 58%, respectively, in epicardial, midmyocardial, and endocardial cells, whereas the rapid component of the delayed rectifier K+ current was not altered. The results indicate that HF remodels electrophysiology in all layers of the left ventricle, and the downregulation of I K1, I to1, and I Ks increases APD and favors occurrence of EADs.

Long-Term Neuromodulatory Regulation of a Motor Pattern–Generating Network: Maintenance of Synaptic Efficacy and Oscillatory Properties

2002 ◽  
Vol 88 (6) ◽  
pp. 2942-2953 ◽  
Author(s):  
Muriel Thoby-Brisson ◽  
John Simmers
Keyword(s):  
Spiny Lobster ◽  
Motor Pattern ◽  
Ionic Currents ◽  
Cell Types ◽  
Delayed Rectifier ◽  
Potential Oscillations ◽  
Calcium Dependent ◽  
Pyloric Network ◽  
Network Maintenance

Rhythm generation by the pyloric motor network in the stomatogastric ganglion (STG) of the spiny lobster requires permissive neuromodulatory inputs from other central ganglia. When these inputs to the STG are suppressed by cutting the single, mainly afferent stomatogastric nerve (stn), pyloric neurons cease to burst and the network falls silent. However, as shown previously, if such a decentralized quiescent ganglion is maintained in organ culture, pyloric network rhythmicity returns after 3–4 days and, although slower, is similar to the motor pattern expressed when the stn is intact. Here we use current- and voltage-clamp, primarily of identified pyloric dilator (PD) neurons, to investigate changes in synaptic and cellular properties that underlie this transition in network behavior. Although the efficacy of chemical synapses between pyloric neurons decreases significantly (by ≤50%) after STG decentralization, the fundamental change leading to rhythm recovery occurs in the voltage-dependent properties of the neurons themselves. Whereas pyloric neurons, including the PD, lateral pyloric, and pyloric cell types, are unable to generate burst-producing membrane potential oscillations in the short-term absence of extrinsic modulatory inputs, in long-term decentralized ganglia, the same cells are able to oscillate spontaneously, even after experimental isolation in situ from all other elements in the pyloric network. In PD neurons this reacquisition of rhythmicity is associated with a net reduction in outward tetraethylammonium-sensitive ionic currents that include a delayed-rectifier type potassium current ( I Kd) and a calcium-dependent K+ current, I KCa. By contrast, long-term STG decentralization caused enhancement of a hyperpolarization-activated inward current that resembles I h. These results are consistent with the hypothesis that modulatory inputs sustain the modulation-dependent rhythmogenic character of the pyloric network by continuously regulating the balance of membrane conductances that underlie neuronal oscillation.

scholarly journals Effects of Sesamin, the Major Furofuran Lignan of Sesame Oil, on the Amplitude and Gating of Voltage-Gated Na+ and K+ Currents

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3062 ◽  
Author(s):  
Ping-Chung Kuo ◽  
Zi-Han Kao ◽  
Shih-Wei Lee ◽  
Sheng-Nan Wu
Keyword(s):  
Ionic Currents ◽  
Sesame Oil ◽  
Delayed Rectifier ◽  
Excitable Cells ◽  
Voltage Gated ◽  
Ic50 Value ◽  
Different Types ◽  
Nav Channels ◽  
Kinetics Of ◽  
K Currents

Sesamin (SSM) and sesamolin (SesA) are the two major furofuran lignans of sesame oil and they have been previously noticed to exert various biological actions. However, their modulatory actions on different types of ionic currents in electrically excitable cells remain largely unresolved. The present experiments were undertaken to explore the possible perturbations of SSM and SesA on different types of ionic currents, e.g., voltage-gated Na+ currents (INa), erg-mediated K+ currents (IK(erg)), M-type K+ currents (IK(M)), delayed-rectifier K+ currents (IK(DR)) and hyperpolarization-activated cation currents (Ih) identified from pituitary tumor (GH3) cells. The exposure to SSM or SesA depressed the transient and late components of INa with different potencies. The IC50 value of SSM needed to lessen the peak or sustained INa was calculated to be 7.2 or 0.6 μM, while that of SesA was 9.8 or 2.5 μM, respectively. The dissociation constant of SSM-perturbed inhibition on INa, based on the first-order reaction scheme, was measured to be 0.93 μM, a value very similar to the IC50 for its depressant action on sustained INa. The addition of SSM was also effective at suppressing the amplitude of resurgent INa. The addition of SSM could concentration-dependently inhibit the IK(M) amplitude with an IC50 value of 4.8 μM. SSM at a concentration of 30 μM could suppress the amplitude of IK(erg), while at 10 μM, it mildly decreased the IK(DR) amplitude. However, the addition of neither SSM (10 μM) nor SesA (10 μM) altered the amplitude or kinetics of Ih in response to long-lasting hyperpolarization. Additionally, in this study, a modified Markovian model designed for SCN8A-encoded (or NaV1.6) channels was implemented to evaluate the plausible modifications of SSM on the gating kinetics of NaV channels. The model demonstrated herein was well suited to predict that the SSM-mediated decrease in peak INa, followed by increased current inactivation, which could largely account for its favorable decrease in the probability of the open-blocked over open state of NaV channels. Collectively, our study provides evidence that highlights the notion that SSM or SesA could block multiple ion currents, such as INa and IK(M), and suggests that these actions are potentially important and may participate in the functional activities of various electrically excitable cells in vivo.

Dopamine Modulation of Honey Bee (Apis mellifera) Antennal-Lobe Neurons

2006 ◽  
Vol 95 (2) ◽  
pp. 1147-1157 ◽  
Author(s):  
Christopher G. Perk ◽  
Alison R. Mercer
Keyword(s):  
Honey Bee ◽  
Adult Development ◽  
Outward Current ◽  
Pupal Stage ◽  
Ionic Currents ◽  
Delayed Rectifier ◽  
Outward Currents ◽  
Sustained Outward Current ◽  
Dopamine Modulation

Primary olfactory centers [antennal lobes (ALs)] of the honey bee brain are invaded by dopamine (DA)-immunoreactive neurons early in development (pupal stage 3), immediately before a period of rapid growth and compartmentalization of the AL neuropil. Here we examine the modulatory actions of DA on honey bee AL neurons during this period. Voltage-clamp recordings in whole cell configuration were used to determine the effects of DA on ionic currents in AL neurons in vitro from pupal bees at stages 4–6 of the nine stages of metamorphic adult development. In ∼45% of the neurons tested, DA (5–50 × 10−5 M) reduced the amplitude of outward currents in the cells. In addition to a slowly activating, sustained outward current, DA reduced the amplitude of a rapidly activating, transient outward conductance in some cells. Both of the currents modulated by DA could be abolished by the removal of Ca2+ from the external medium or by treatment of cells with charybdotoxin (2 × 10−8 M), a blocker of Ca2+-dependent K+ currents in the cells. Ca2+ currents were not affected by DA, nor were A-type K+ currents ( IA). Results suggest that the delayed rectifier-like current ( IKV) also remains intact in the presence of DA. Taken together, our data indicate that Ca2+-dependent K+ currents are targets of DA modulation in honey bee AL neurons. This study lends support to the hypothesis that DA plays a role in the developing brain of the bee.

Ionic currents of the lateral pyloric neuron of the stomatogastric ganglion of the crab

1992 ◽  
Vol 67 (2) ◽  
pp. 318-331 ◽  
Author(s):  
J. Golowasch ◽  
E. Marder
Keyword(s):  
Ionic Currents ◽  
Stomatogastric Ganglion ◽  
Delayed Rectifier ◽  
Delayed Rectifier Current ◽  
Outward Currents ◽  
Ionic Conductances ◽  
Voltage Dependent ◽  
Inward Currents ◽  
K Current ◽  
Direct Target

1. The lateral pyloric (LP) neuron is an important component of the network that generates the pyloric rhythm of the stomatogastric ganglion (STG) and is a direct target of many modulatory inputs to the STG. Our aim in this and the subsequent two papers is to describe the conductances present in this cell and to understand the role these conductances play in shaping the activity of the neuron. 2. LP neurons were studied in two-electrode voltage clamp (TEVC) in a saline solution containing tetrodotoxin (TTX) and picrotoxin (PTX) to isolate them pharmacologically from presynaptic inputs. 3. We identified six voltage-dependent ionic conductances. These include three outward currents that resemble a delayed rectifier current, a Ca(2+)-activated K+ current and an A-current similar to those seen in many other preparations. LP neurons show three inward currents, a fast TTX-sensitive current, a hyperpolarization-activated inward current, and a Ca2+ current.

Similar Properties of Transient, Persistent, and Resurgent Na Currents in GABAergic and Non-GABAergic Vestibular Nucleus Neurons

2008 ◽  
Vol 99 (5) ◽  
pp. 2060-2065 ◽  
Author(s):  
Aryn H. Gittis ◽  
Sascha du Lac
Keyword(s):  
Transgenic Mice ◽  
Vestibular Nucleus ◽  
Vestibular Nuclei ◽  
Gabaergic Neurons ◽  
Firing Rates ◽  
Na Currents ◽  
Voltage Dependent ◽  
Firing Properties ◽  
K Currents ◽  
Fast Firing

Sodium currents in fast firing neurons are tuned to support sustained firing rates >50–60 Hz. This is typically accomplished with fast channel kinetics and the ability to minimize the accumulation of Na channels into inactivated states. Neurons in the medial vestibular nuclei (MVN) can fire at exceptionally high rates, but their Na currents have never been characterized. In this study, Na current kinetics and voltage-dependent properties were compared in two classes of MVN neurons with distinct firing properties. Non-GABAergic neurons (fluorescently labeled in YFP-16 transgenic mice) have action potentials with faster rise and fall kinetics and sustain higher firing rates than GABAergic neurons (fluorescently labeled in GIN transgenic mice). A previous study showed that these neurons express a differential balance of K currents. To determine whether the Na currents in these two populations were different, their kinetics and voltage-dependent properties were measured in acutely dissociated neurons from 24- to 40-day-old mice. All neurons expressed persistent Na currents and large transient Na currents with resurgent kinetics tuned for fast firing. No differences were found between the Na currents expressed in GABAergic and non-GABAergic MVN neurons, suggesting that differences in properties of these neurons are tuned by their K currents.

Electrophysiological characterization and computational models of HVC neurons in the zebra finch

2013 ◽  
Vol 110 (5) ◽  
pp. 1227-1245 ◽  
Author(s):  
Arij Daou ◽  
Matthew T. Ross ◽  
Frank Johnson ◽  
Richard L. Hyson ◽  
Richard Bertram
Keyword(s):  
Computational Models ◽  
Premotor Cortex ◽  
Brain Slices ◽  
Ionic Currents ◽  
Proper Name ◽  
Using Data ◽  
Electrophysiological Characterization

The nucleus HVC (proper name) within the avian analog of mammal premotor cortex produces stereotyped instructions through the motor pathway leading to precise, learned vocalization by songbirds. Electrophysiological characterization of component HVC neurons is an important requirement in building a model to understand HVC function. The HVC contains three neural populations: neurons that project to the RA (robust nucleus of arcopallium), neurons that project to Area X (of the avian basal ganglia), and interneurons. These three populations are interconnected with specific patterns of excitatory and inhibitory connectivity, and they fire with characteristic patterns both in vivo and in vitro. We performed whole cell current-clamp recordings on HVC neurons within brain slices to examine their intrinsic firing properties and determine which ionic currents are responsible for their characteristic firing patterns. We also developed conductance-based models for the different neurons and calibrated the models using data from our brain slice work. These models were then used to generate predictions about the makeup of the ionic currents that are responsible for the different responses to stimuli. These predictions were then tested and verified in the slice using pharmacological manipulations. The model and the slice work highlight roles of a hyperpolarization-activated inward current ( Ih), a low-threshold T-type Ca2+ current ( ICa-T), an A-type K+ current ( IA), a Ca2+-activated K+ current ( ISK), and a Na+-dependent K+ current ( IKNa) in driving the characteristic neural patterns observed in the three HVC neuronal populations. The result is an improved characterization of the HVC neurons responsible for song production in the songbird.

Differentiation of two mouse cell lines is associated with hypomethylation of their genomes

1984 ◽  
Vol 4 (9) ◽  
pp. 1800-1806
Author(s):  
T H Bestor ◽  
S B Hellewell ◽  
V M Ingram
Keyword(s):  
Dna Methyltransferase ◽  
Cell Types ◽  
Mouse Cell ◽  
F9 Cells ◽  
Dna Restriction Fragments ◽  
Dna Restriction ◽  
F9 Embryonal Carcinoma Cells ◽  
Murine Erythroleukemia ◽  
Kinetics Of

Methyl-accepting assays and a sensitive method for labeling specific CpG sites have been used to show that the DNA of F9 embryonal carcinoma cells decreases in 5-methylcytosine content by ca. 9% during retinoic acid-induced differentiation, whereas the DNA of dimethyl sulfoxide-induced Friend murine erythroleukemia (MEL) cells loses ca. 3.8% of its methyl groups. These values correspond to the demethylation of 2.2 X 10(6) and 0.9 X 10(6) 5'-CpG-3' sites per haploid genome in differentiating F9 and MEL cells, respectively. Fluorography of DNA restriction fragments methylated in vitro and displayed on agarose gels showed that demethylation occurred throughout the genome. In uninduced F9 cells, the sequence TCGA tended to be more heavily methylated than did the sequence CCGG, whereas this tendency was reversed in MEL cells. The kinetics of in vitro DNA methylation reactions catalyzed by MEL cell DNA methyltransferase showed that substantial numbers of hemimethylated sites accumulate in the DNA of terminally differentiating F9 and MEL cells, implying that a partial loss of DNA-methylating activity may accompany terminal differentiation in these two cell types.

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