bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycine‐activated currents are changed by coincident membrane depolarization in developing rat auditory brainstem neurones
Authors: Backus Kurt H. , Deitmer Joachim W. , Friauf Eckhard 
Published: September 2004

During early ontogeny, glycine receptors (GlyRs) exert depolarizing responses which may be of developmental relevance. We have used the gramicidin‐perforated patch technique to elucidate the mechanism of glycine‐activated currents in developing neurones of the rat lateral superior olive (LSO).
When the holding potential was set to −60 mV, perforated‐patch recordings revealed glycine‐induced inward currents in 59 %, outward currents in 5 % and biphasic currents in 34 % of the LSO neurones tested (n= 44). The biphasic currents were characterized by a transient outward phase which was followed by an inward phase.
Ion substitution experiments showed that both Cl− and HCO3− contributed to the glycine‐ induced biphasic current responses.
In the biphasic responses, the reversal potential of the glycine‐induced current (Egly) depended on the response phase. A strong shift of Egly from a mean of −72 mV during the outward phase of the glycine response to a mean of −51 mV during the inward phase was observed, suggesting a shift of an ion gradient.
When the membrane potential was depolarized, ‘tail’ currents were induced in the presence of glycine. An increased duration or amplitude of the evoked depolarizations resulted in a proportional enlargement of these tail currents, indicating that they were produced by a shift of an ion gradient. Since changes of the HCO3− gradient are negligible, because of the carbonic anhydrase activity, we suggest that these tail currents were caused by a shift of the Cl− gradient.
We conclude that Cl− accumulates intracellularly during the activation of GlyRs and, consequently, Egly moves towards more positive values.
Coincident depolarizing stimuli enhanced intracellular Cl− accumulation and the shift of Egly, thereby switching hyperpolarizing to depolarizing action. This change could assist in an activity‐dependent strengthening and refinement of glycinergic synapses during the maturation of inhibitory connectivity.
μ‐Opioid receptor activation inhibits N‐ and P‐type Ca2+ channel currents in magnocellular neurones of the rat supraoptic nucleus
Authors: Soldo Brandi L. , Moises Hylan C. 
Published: September 2004

The whole‐cell voltage‐clamp technique was used to examine opioid regulation of Ba2+ currents (IBa) through voltage‐sensitive Ca2+ channels in isolated magnocellular supraoptic neurones (MNCs). The effects of local application of μ‐, δ‐ or κ‐opioid receptor selective agonists were examined on specific components of high voltage‐activated (HVA) IBa, pharmacologically isolated by use of Ca2+ channel‐subtype selective antagonists.
The μ‐opioid receptor selective agonist, DAMGO, suppressed HVA IBa (in 64/71 neurones) in a naloxone‐reversible and concentration‐dependent manner (EC50= 170 nm, Emax= 19.5 %). The DAMGO‐induced inhibition was rapid in onset, associated with kinetic slowing and voltage dependent, being reversed by strong depolarizing prepulses. Low‐voltage activated (LVA) IBa was not modulated by DAMGO.
Administration of κ‐ (U69 593) or δ‐selective (DPDPE) opioid receptor agonists did not affect IBa. However, immunostaining of permeabilized MNCs with an antibody specific for κ1‐opioid receptors revealed the presence of this opioid receptor subtype in a large number of isolated somata.
μ‐Opioid‐induced inhibition in IBa was largely abolished after blockade of N‐type and P‐type channel currents by ω‐conotoxin GVIA (1 μm) and ω‐agatoxin IVA (100 nm), respectively. Quantitation of antagonist effects on DAMGO‐induced reductions in IBa revealed that N‐ and P‐type channels contributed roughly equally to the μ‐opioid sensitive portion of total IBa.
These results indicate that μ‐opioid receptors are negatively coupled to N‐ and P‐type Ca2+ channels in the somatodendritic regions of MNCs, possibly via a membrane‐delimited G‐protein‐dependent pathway. They also support a scheme in which opioids may act in part to modulate cellular activity and regulate neurosecretory function by their direct action on the neuroendocrine neurones of the hypothalamic supraoptic neucleus.
Synaptic inhibition: its role in suprachiasmatic nucleus neuronal thermosensitivity and temperature compensation in the rat
Authors: Burgoon P. W. , Boulant J. A. 
Published: September 2004

Whole‐cell patch clamp recordings of neurones in the suprachiasmatic nucleus (SCN) from rat brain slices were analysed for changes in spontaneous synaptic activity during changes in temperature. While recent studies have identified temperature‐sensitive responses in some SCN neurones, it is not known whether or how thermal information can be communicated through SCN neural networks, particularly since biological clocks such as the SCN are assumed to be temperature compensated.
Synaptic activity was predominantly inhibitory and mediated through GABAA receptor activation. Spontaneous inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) were usually blocked with perifusion of 10–50 μm bicuculline methiodide (BMI). BMI was used to test hypotheses that inhibitory synapses are capable of either enhancing or suppressing the thermosensitivity of SCN neurones.
Temperature had opposite effects on the amplitude of IPSPs and IPSCs. Warming decreased IPSP amplitude but increased IPSC amplitude. This suggests that thermally induced changes in IPSP amplitude are primarily influenced by resistance changes in the postsynaptic membrane. The thermal effect on IPSP amplitude contributed to an enhancement of thermosensitivity in some neurones.
In many SCN neurones, temperature affected the frequency of IPSPs and IPSCs. An increase in IPSP frequency with warming and a decrease in frequency during cooling made several SCN neurones temperature insensitive, allowing these neurones to maintain a relatively constant firing rate during changes in temperature. This temperature‐adjusted change in synaptic frequency provides a mechanism of temperature compensation in the rat SCN.
Inhibitory control of plateau properties in dorsal horn neurones in the turtle spinal cord in vitro
Authors: Russo Raúl E. , Nagy Frédéric , Hounsgaard Jørn 
Published: September 2004

The role of inhibition in control of plateau‐generating neurones in the dorsal horn was studied in an in vitro preparation of the spinal cord of the turtle. Ionotropic and metabotropic inhibition was found to condition the expression of plateau potentials.
Blockade of γ‐aminobutyric acid (GABAA) and glycine receptors by their selective antagonists bicuculline (10‐50 μM) and strychnine (5‐20 μM) enhanced the excitatory response to stimulation of the dorsal root and facilitated the expression of plateau potentials.
Bicuculline and strychnine also facilitated the generation of plateau potentials in response to depolarizing current pulses, suggesting the presence of tonic ionotropic inhibitory mechanisms in turtle spinal cord slices.
Activation of GABAB receptors also inhibited plateau‐generating neurones. The selective agonist baclofen (5‐50 μM) inhibited wind‐up of the response to repeated depolarizations induced synaptically or by intracellular current pulses.
Baclofen reduced afferent synaptic input. This effect was not affected by bicuculline or strychnine and was blocked by the selective GABAB receptor antagonist 2‐hydroxysaclofen (2‐OH‐saclofen, 100‐400 μM).
Postsynaptically, baclofen inhibited plateau properties. Activation of GABAB receptors produced a hyperpolarization (7.0 ± 0.5 mV, mean ± s.e.m., n= 29) with an associated decrease in input resistance (22.7 ± 3.1 %, n= 24). These effects were blocked by extracellular Ba2+ (1‐2 mM).
When the baclofen‐induced hyperpolarization and shunt were compensated for by adjusting the bias current and the strength of the stimulus, baclofen still inhibited generation of plateau potentials. Wind‐up and after‐discharges were also inhibited by baclofen. These effects remained in the presence of tetrodotoxin (1 μM) and were antagonized by 2‐OH‐saclofen.
The inhibition of plateau properties was observed even when the baclofen‐induced hyperpolarization and shunt were blocked by Ba2+ and when potassium channels were blocked by Ba2+ (3 mM), tetraethylammonium (TEA, 15 mM) and apamin (0.25‐0.5 μM). The baclofen‐sensitive component of the plateau potential was reduced by nifedipine (10 μM), suggesting a modulation of postsynaptic L‐type Ca2+ channels.
We suggest that inhibitory regulation of plateau properties plays a role in somatosensory processing in the dorsal horn. The inhibitory control of wind‐up and after‐discharges may be particularly significant in physiological and therapeutic control of central sensitization to pain.
The influence of corticofugal feedback on the temporal structure of visual responses of cat thalamic relay cells
Authors: Wörgötter F. , Nelle E. , Li B. , Funke K. 
Published: September 2004

Visually driven single‐unit activity was recorded in the dorsal lateral geniculate nucleus (dLGN) of the anaesthetized cat while inactivating or stimulating the corticofugal feedback from area 17/18 by means of cortical cooling or application of GABA (inactivation), or application of glutamate or quisqualate (Glu, Quis; stimulation) to layer VI.
Manipulations of the corticofugal feedback primarily affected the multimodal interspike interval pattern previously reported to be present in the tonic component of visual responses elicited by spot‐like stimuli.
Sixty‐three per cent of all neurons could be influenced, and temporally localized interspike interval distributions were measured which commonly consisted of one fundamentalinterval peak (leftmost peak) and integer multiples thereof (higher orderpeaks). During blockade of the corticofugal feedback, interspike intervals were redistributed into the higher order peaks in about 70 % of the cases, accompanied by a reduced mean firing rate. During stimulation the reverse effect occurred in 69 % of cases.
Increased synchronization of the EEG (increased power in the δ‐wave range, 1‐4 Hz) had an effect similar to cortex inactivation. The specificity of corticofugal effects was verified by consideration of these EEG effects and by dLGN double recordings with one dLGN cell topographically matched with the cortical inactivation/activation site and the second cell outside this area. Clear effects due to manipulation of the corticofugal feedback were found only for the matched dLGN site.
In addition we observed that the peaks of the interval distributions were narrower during active corticofugal feedback, such that the temporal dispersion of the signal transmission to the cortex was reduced.
The mechanisms underlying this effect were further analysed in a biophysically realistic model demonstrating that the timing of the spikes in the dLGN is improved as soon as the cortical feedback is active. The high degree of convergence/divergence between neurons along the closed feedback loop thereby leads to a temporal averaging effect which reduces the interval dispersion and also introduces synchronization between dLGN cells.
Such a mechanism may thus counteract the deterioration of spike timing accuracy which would otherwise occur as a consequence of synaptic noise and other uncorrelated sources of activity at a given neuron.
Properties of voltage‐activated [Ca2+]i transients in single smooth muscle cells isolated from pregnant rat uterus
Authors: Shmigol A. V. , Eisner D. A. , Wray Susan 
Published: September 2004

The intracellular calcium concentration ([Ca2+]i) was measured at 35 °C using the fluorescent indicator indo‐1 in patch‐clamped, single uterine myocytes from pregnant rats to investigate the relationship between depolarization, Ca2+ current (ICa) and [Ca2+]i.
Membrane depolarization activated ICa and produced a [Ca2+]i transient. The rapid increase in [Ca2+]i occurred at the same time as the inward ICa. Both ICa and the increase in [Ca2+]i were abolished by nifedipine (10 μm).
When the membrane potential was held at ‐80 mV the threshold depolarization for an increase in [Ca2+]i was about ‐55 to ‐50 mV. As the magnitude of the depolarization was increased to about 0 mV there was an increase in the size of both ICa and the increase in [Ca2+]i. As the magnitude of the depolarization was further increased both ICa and the [Ca2+]i increase declined.
When the depolarizing pulses were applied at 3 Hz to mimic normal action potentials then the individual [Ca2+]i transients did not fully relax and a tetanic rise of [Ca2+]i was observed. Under these conditions, there was not a simple relationship between the magnitude of the Ca2+ response and Ca2+ entry. When pairs of depolarizing pulses were applied, the increase in [Ca2+]i produced by the second pulse was larger (in relation to the magnitude of the L‐type Ca2+ current) than that produced by the first pulse. This facilitation was abolished by both ryanodine and cyclopiazonic acid suggesting a role for release from intracellular stores.
We conclude that the L‐type Ca2+ current is the major source of Ca2+ ions entering the cell to produce the [Ca2+]i transient on depolarization. The magnitude of the increase in [Ca2+]i may, however, be amplified by Ca2+‐induced Ca2+ release.
Presynaptic inhibition by dopamine of a discrete component of GABA release in rat substantia nigra pars reticulata
Authors: Miyazaki Takefumi , Lacey Michael G. 
Published: September 2004

Whole‐cell patch clamp recordings were made from substantia nigra pars reticulata (SNr) neurones in rat midbrain slices. Monosynaptic IPSCs were evoked by electrical stimulation of the cerebral peduncle in the presence of the glutamate receptor antagonists CNQX (6‐cyano‐7‐nitroquinoxaline‐2,3‐dione) and AP5 (2‐amino‐5‐phosphonopentanoic acid).
IPSCs were predominantly outward at −70 mV (in 124/135 cells), with a reversal potential of −83 mV, a time to peak of 2.6 ms and a decay time constant of 6.5 ms. Faster inward IPSCs were also observed in thirty‐five cells, with a time to peak of 1.0 ms, a decay time constant of 2.3 ms, and a reversal potential of −61 mV. Both IPSCs were sensitive to the GABAA receptor antagonists picrotoxin or bicuculline.
In cells recorded with Cs+‐filled pipettes, the outward IPSC reversal potential was shifted to −76 mV, closer to the estimated Cl− equilibrium potential of −56 mV, while that of the inward IPSC was unchanged at −64 mV.
The outward IPSC was reversibly depressed by up to 100 % by dopamine in a concentration‐dependent manner with an IC50 of 10.5 μm, while the inward IPSC was relatively insensitive.
Dopamine was without effect on cell holding current, or on outward IPSC reversal potential, but it increased paired‐pulse IPSC facilitation, consistent with a presynaptic site of action.
The D1‐like dopamine receptor agonist SKF 38393 (10 μm) depressed the outward IPSC by 43 %, while the D2‐like dopamine receptor agonist quinpirole (10 μm) was without effect.
It is concluded that GABA‐ergic synaptic input onto distal rather than proximal regions of SNr neurones is susceptible to presynaptic inhibition via a D1‐like receptor. These inputs are probably from striato‐nigral fibres, and their inhibition by dopamine is likely to influence the patterning of basal ganglia output.
Expression of functional GABAA receptors in cholecystokinin‐secreting gut neuroendocrine murine STC‐1 cells
Authors: Glassmeier G. , Herzig K.‐H. , Höpfner M. , Lemmer K. , Jansen A. , Scherübl H. 
Published: September 2004

Gastrointestinal neuroendocrine (NE) cells synthesize, store and secrete γ‐aminobutyric acid (GABA). Recently, an autocrine‐paracrine function of GABA has been proposed for secretion from NE cells.
To search for functional GABAA receptors in NE gut cells, we performed whole‐cell and perforated‐patch‐clamp studies in the intestinal cholecystokinin (CCK)‐secreting NE cell line STC‐1.
Application of GABA evoked currents in STC‐1 cells. These effects were mimicked by muscimol, an agonist of GABAA receptors, and blocked by picrotoxin or bicuculline, antagonists of GABAA receptors. The GABA‐ or muscimol‐activated currents reversed near 0 mV, which under the recording conditions used was consistent with the activation of the GABAA receptor‐Cl− channel complex.
In contrast to the effect on most neurons, GABA as well as muscimol led to a (reversible) depolarization of the membrane potential of STC‐1 cells. Membrane depolarization in turn activated voltage‐gated Ca2+ channels and increased intracellular Ca2+ concentrations in STC‐1 cells.
In accordance with the observed membrane depolarization and activation of voltage‐gated Ca2+ channels, both GABA and muscimol stimulated Ca2+‐dependent CCK release. In contrast, bicuculline inhibited the GABA‐induced secretion of CCK.
Using the reverse transcription‐polymerase chain reaction (RT‐PCR), mRNA of the GABAA receptor subunits α2, α3, α5, β1, β3 and δ could be detected in STC‐1 cells.
In summary, we have shown that the CCK‐secreting gut NE cell line STC‐1 expresses functional GABAA receptors and that GABA stimulates CCK release. Thus, GABA is involved in the fine tuning of CCK secretion from the gut NE cell line STC‐1.
Persistent depolarizing action of GABA in rat Cajal‐Retzius cells
Authors: Mienville Jean‐Marc 
Published: September 2004

To characterize membrane properties that might be relevant to the function and fate of Cajal‐Retzius (CR) cells, the pharmacological and physiological effects of GABA acting at GABAA receptors were studied in CR cells from embryonic (E18) and postnatal (P11–13) slices of rat neocortex.
From the embryonic to the postnatal stage, GABA‐induced maximum current almost tripled, the EC50 increased from 38 to 74 μm, and the Hill number increased from 1.4 to 1.9. Muscimol‐elicited currents were qualitatively and quantitatively similar to those produced by GABA.
GABA‐induced changes in the amplitude of large‐conductance Ca2+‐activated K+ channel current recorded on‐cell from E18 CR cells were consistent with depolarization.
GABA‐mediated depolarization of embryonic and postnatal CR cells was studied directly with perforated‐patch recording techniques. Ten micromolar and 1 mm GABA, respectively, depolarized E18 CR cells to −27 ± 1 and −25 ± 3 mV. These same concentrations of GABA depolarized P11 CR cells to −36 ± 3 and −23 ± 3 mV.
In postnatal cortex, GABA (100 μm) increased the firing rate of CR cells 7.3‐fold. By contrast, the firing of hippocampal pyramidal cells from slices of the same age (P12) was totally and reversibly blocked by GABA.
These experiments suggest that contrary to its postnatal inhibitory shift observed in other cells, the depolarizing effect of GABA remains in CR cells from E18 until their virtual disappearance.
Leukemia inhibitory factor induces sympathetic sprouting in intact dorsal root ganglia in the adult rat in vivo
Authors: Thompson Stephen W. N. , Majithia Anooj A. 
Published: September 2004

The role of the cytokine leukemia inhibitory factor (LIF) in axotomy‐induced sprouting of postganglionic sympathetic fibres into the dorsal root ganglia was examined in the adult rat.
Immunocytochemistry was used to study the distribution and density of tyrosine hydroxylase‐immunoreactive (TH‐IR) fibres within the lumbar dorsal root ganglia and lumbar spinal nerves 14 days following continuous intrathecal infusion of LIF (0.33 mg ml−1), or 14 days following unilateral peripheral nerve axotomy.
In LIF‐treated animals, numerous pericellular TH‐IR basket‐like structures were observed surrounding sensory neurones, which were absent from controls.
The number of TH‐IR fibres within the L3, L4 and L5 spinal nerves was significantly higher in LIF‐treated animals than in control or saline‐treated animals (P < 0.01, Student's t test).
Unilateral ligation of the L4 spinal nerve or unilateral sciatic nerve ligation was also associated with the formation of TH‐IR baskets around sensory neurones and a significant increase in the number of TH‐IR fibres within the lumbar spinal nerves (P < 0.01, Student's t test).
The percentage of neurones surrounded by TH‐IR baskets within the L3 and L4 dorsal root ganglia following sciatic axotomy was significantly reduced in animals treated continuously for 2 weeks with a monoclonal antibody against the LIF receptor motif, gp130 (0.833 mg ml−1) (P < 0.05, Mann‐Whitney U test). Antibody treatment did not reduce the axotomy‐induced increase in TH‐IR fibres within lumbar spinal nerves.
These results demonstrate that exogenous application of the axotomy‐associated cytokine LIF is associated with sprouting of uninjured postganglionic sympathetic neurones around sensory neurones within the dorsal root ganglion. It is likely that increased LIF expression following peripheral axotomy plays an important role in the novel sympathetic sprouting observed within sensory ganglia following peripheral nerve injury.
Nitric oxide mediates contraction‐induced attenuation of sympathetic vasoconstriction in rat skeletal muscle
Authors: Thomas Gail D. , Victor Ronald G. 
Published: September 2004

Sympathetic vasoconstriction is attenuated by metabolic events in contracting rat skeletal muscle, in part by activation of ATP‐sensitive potassium (KATP) channels. However, the specific metabolites in contracting muscle that open KATPchannels are not known. We therefore asked if contraction‐induced attenuation of sympathetic vasoconstriction is mediated by the endogenous vasodilators nitric oxide (NO), adenosine, or prostaglandins PGI2or PGE2, all of which are putative KATPchannel openers.In anaesthetized rats, hindlimb contraction alone significantly attenuated the vasoconstrictor responses to lumbar sympathetic nerve stimulation. Inhibition of NO synthase withN‐nitro‐L‐arginine methyl ester (L‐NAME, 5 mg kg−1, i.v.) partially reversed this effect of contraction, resulting in enhanced sympathetic vasoconstriction in contracting hindlimb. Subsequent treatment with the KATPchannel blocker glibenclamide (20 mg kg−1, i.v.) had no further effect on sympathetic vasoconstriction in contracting hindlimb.This effect of L‐NAME to partially reverse contraction‐induced attenuation of sympathetic vasoconstriction was not replicated by D‐NAME (5 mg kg−1, i.v.) or angiotensin II (12.5 ng kg−1min−1, i.v.), the latter used as a hypertensive control.Adenosine receptor blockade with 8‐(p‐sulphophenyl)theophylline (10 mg kg−1, i.v.) or cyclooxygenase inhibition with indomethacin (5 mg kg−1, i.v.) had no effect on contraction‐induced attenuation of sympathetic vasoconstriction.These results suggest that NO plays an important role in the precise regulation of blood flow in exercising skeletal muscles by opposing sympathetic vasoconstriction. Although the underlying mechanism is not known, it may involve NO‐induced activation of vascular KATPchannels.