Biomedical subjects

M Martina

Publications and source records attributed to M Martina.

At least 19 recordsLinked to original sources

PubMed2001

Changes in extracellular Ca2+ can affect the pattern of discharge in rat thalamic neurons.

1. The aim of this study was to investigate some of the cellular mechanisms involved in the effects caused by changes in extracellular Ca2+ concentration ([Ca2+](o)). 2. Current- and voltage-clamp experiments were carried out on acutely isolated thalamic neurons of rats. 3. Increasing [Ca2+](o) alone induced a transition of the discharge from single spike to burst mode in isolated current-clamped neurons. 4. Increasing [Ca(2+)](o) caused the voltage-dependent characteristics of the low voltage-activated (LVA) transient Ca2+ currents to shift towards positive values on the voltage axis. Changing [Ca2+](o) from 0.5 to 5 mM caused the inactivation curve to shift by 21 mV. 5. Extracellular Ca2+ blocked a steady cationic current. This current reversed at -35 mV, was scarcely affected by Mg2+ and was completely blocked by the non-selective cation channel inhibitor gadolinium (10 microM). The effect of [Ca2+](o) was mimicked by 500 microM spermine, a polyamine which acts as an agonist for the Ca(2+)-sensing receptor, and was modulated by intracellular GTP-gamma-S. 6. At the resting potential, both the voltage shift and the block of the inward current removed the inactivation of LVA calcium channels and, together with the increase in the Ca2+ driving force, favoured a rise in the low threshold Ca2+ spikes, causing the thalamic firing to change to the oscillatory mode. 7. Our data indicate that [Ca2+](o) is involved in multiple mechanisms of control of the thalamic relay and pacemaker activity. These findings shed light on the correlation between hypercalcaemia, low frequency EEG activity and symptoms such as sleepiness and lethargy described in many clinical papers.

Animals↗

PubMed2001

Propagation of neocortical inputs in the perirhinal cortex.

The perirhinal area is a rostrocaudally oriented strip of cortex in which lesions produce memory and perceptual impairments. It receives topographically organized transverse projections from associative neocortical areas and is endowed with intrinsic longitudinal connections that could distribute neocortical inputs in the rostrocaudal axis. In search of distinguishing network properties that might support perirhinal involvement in memory, we have performed whole-cell recordings in horizontal perirhinal slices with preserved transverse neocortical links and intrinsic longitudinal connections. Neocortical stimulation sites in rostrocaudal register with regular spiking perirhinal neurons elicited a sequence of excitatory and inhibitory synaptic potentials. In contrast, apparently pure excitatory responses were observed when the stimulating and recording sites were separated by >/=1 mm in the rostrocaudal axis. This suggested that adjacent and distant neocortical stimuli influence regular spiking perirhinal neurons by pathways that respectively form and do not form synapses with inhibitory interneurons. In keeping with this, presumed interneurons did not respond to distant neocortical stimuli. These results suggest that neocortical inputs recruit perirhinal inhibitory interneurons located at the same transverse level, limiting the depolarization of principal perirhinal cells. In contrast, distant neocortical inputs only evoke excitation because longitudinal perirhinal pathways do not engage inhibitory interneurons. This leads us to suggest that the perirhinal network is biased to favor Hebbian-like associative interactions between coincident and spatially distributed inputs.

Action Potentials↗

PubMed2001

Cell-type-specific GABA responses and chloride homeostasis in the cortex and amygdala.

The GABA responses of fast-spiking (FS) interneurons and regular-spiking (RS) principal cells were studied using whole cell and perforated-patch recordings in slices of the basolateral amygdala, neo-, and perirhinal cortex. In these three areas, responses to exogenous and synaptically released GABA were abolished by GABA(A) receptor antagonists in FS cells but also included a GABA(B) component in RS cells. Moreover, E(GABA(A)) of FS and RS cells differed from the calculated E(Cl) (-61 mV), but in opposite direction (FS, -54 mV; RS, -72 mV). This was not due to a differential dialysis of FS and RS cells by the pipette solution because the discrepancy persisted when recordings were obtained with the perforated-patch-clamp technique, using the cation-selective ionophore gramicidin. Moreover, pharmacological inhibition of cation-chloride cotransporters revealed that the differing E(GABA(A)) of FS and RS neurons arises from cell-type-specific chloride homeostatic mechanisms. Indeed, the prevalent regulators of the intracellular chloride concentration are cotransporters that accumulate chloride in FS cells and extrude chloride in RS neurons. Thus, our results suggest that in the basolateral amygdala as well as in the parietal and perirhinal cortices, FS interneurons are more excitable than principal cells not only by virtue of their dissimilar electroresponsive properties but also because they express a different complement of GABA receptors and chloride homeostatic mechanisms.

Amygdala↗

PubMed2000

Bistable behavior of inhibitory neurons controlling impulse traffic through the amygdala: role of a slowly deinactivating K+ current.

The intercalated cell masses of the amygdala are clusters of GABAergic neurons located strategically to influence behavioral responsiveness. Indeed, they receive glutamatergic sensory inputs from the basolateral amygdaloid complex and generate feedforward inhibition in neurons of the central amygdala that mediate important components of fear responses. In the present study, using whole-cell recording methods in coronal slices of the guinea pig amygdala, we show that the activity of intercalated neurons is a function of their recent firing history because they express an unusual voltage-dependent K(+) conductance (termed I(SD) for slowly deinactivating). This conductance activates in the subthreshold regime, inactivates in response to suprathreshold depolarizations, and deinactivates very slowly upon return to rest. As a result, after bouts of suprathreshold activity, these cells enter a self-sustaining state of heightened excitability associated with an increased input resistance and a membrane depolarization. In turn, these changes increase the likelihood that ongoing synaptic activity will trigger orthodromic action potentials. However, because each orthodromic spike "renews" the inactivation of I(SD), intercalated cells can remain hyperexcitable for a long time and, via the central amygdaloid nucleus, exert a lasting influence on behavior.

Action Potentials↗

PubMed2000

Distal initiation and active propagation of action potentials in interneuron dendrites.

Fast and reliable activation of inhibitory interneurons is critical for the stability of cortical neuronal networks. Active conductances in dendrites may facilitate interneuron activation, but direct experimental evidence was unavailable. Patch-clamp recordings from dendrites of hippocampal oriens-alveus interneurons revealed high densities of voltage-gated sodium and potassium ion channels. Simultaneous recordings from dendrites and somata suggested that action potential initiation occurs preferentially in the axon with long threshold stimuli, but can be shifted to somatodendritic sites when brief stimuli are applied. After initiation, action potentials propagate over the somatodendritic domain with constant amplitude, high velocity, and reliability, even during high-frequency trains.

Action Potentials↗

PubMed2000

Polarized synaptic interactions between intercalated neurons of the amygdala.

The intercalated (ITC) cell masses are small GABAergic cell clusters interposed between the basolateral (BL) complex and central (CE) nucleus of the amygdala. ITC cells receive excitatory afferents from the BL complex and generate feed-forward inhibition in the CE nucleus. Recently it was shown that ITC cells could gate impulse traffic between the BL complex and CE nucleus in a spatiotemporally differentiated manner. In addition, it was hypothesized that lateromedial inhibitory interactions between different ITC cell clusters played a critical role in this respect. Given the potential importance of such conditional computations, the present study aimed to characterize the connectivity existing among ITC cells. To this end, whole cell recordings of ITC neurons were obtained under visual guidance in coronal slices of the guinea pig amygdala. Electrical stimuli applied in the BL complex primarily elicited excitatory responses when they were applied at the same lateromedial level or more medially than the recorded ITC cells. As the stimulation site was moved laterally, the character of the response shifted toward inhibition. Both bicuculline and non-N-methyl-D-aspartate receptor antagonists abolished this BL-evoked inhibition, suggesting that it was not mediated by BL inhibitory cells projecting to ITC neurons. In keeping with this, local glutamate injections in and around the ITC clusters revealed that the most effective site to inhibit ITC cells were ITC clusters located laterally with respect to the recorded one. The activation of more medial ITC clusters evoked much smaller responses. Thus, connections between ITC clusters tend to run in a lateromedial direction. To identify the source of these directionally polarized synaptic interactions, the morphological features of ITC cells were analyzed by intracellular injection of Neurobiotin. This analysis revealed that the dendritic tree and axonal arbor of ITC cells are asymmetric in the lateromedial plane. In particular, their laterally directed dendrites were longer than the medial ones, whereas their laterally directed axon collaterals were shorter than the medial ones. It is concluded that the morphological asymmetry of ITC cells accounts for the directional polarization of inter-ITC connections. The significance of these findings for the gating of information transfer from the BL complex to the CE nucleus is discussed.

Amygdala↗

PubMed1999

An inhibitory interface gates impulse traffic between the input and output stations of the amygdala.

The central amygdaloid nucleus projects to brainstem and hypothalamic nuclei mediating fear responses and receives convergent sensory inputs from the basolateral amygdaloid complex. However, interposed between the basolateral complex and central nucleus is a string of interconnected GABAergic cell clusters, the intercalated cell masses. Here, we analyzed how intercalated neurons influence impulse traffic between the basolateral complex and central nucleus using whole-cell recordings, microstimulation, and local application of glutamate receptor antagonists in brain slices. Our results suggest that intercalated neurons receive glutamatergic inputs from the basolateral complex and generate feedforward inhibition in neurons of the central nucleus. As the position of the recording site was shifted medially, intercalated cells projected to gradually more medial sectors of the central nucleus and were maximally responsive to progressively more medial stimulation sites in the basolateral complex. Thus, there is a lateromedial correspondence between the position of intercalated cells, their projection site in the central nucleus, and the source of their excitatory afferents in the basolateral complex. In addition, basolateral stimulation sites eliciting maximal excitatory responses in intercalated neurons were flanked laterally by sites eliciting prevalently inhibitory responses via the activation of intercalated cells located more laterally. As a result, the feedforward inhibition generated by intercalated neurons and, indirectly, the amplitude of the responses of central neurons could be increased or decreased depending on which combination of amygdala nuclei are activated and in what sequence. Thus, the output of the central nucleus depends not only on the nature and intensity of sensory inputs but also on their timing and origin.

Afferent Pathways↗

PubMed1999

Physiological properties of central medial and central lateral amygdala neurons.

Mounting evidence implicates the central (CE) nucleus of the amygdala in the mediation of classically conditioned fear responses. However, little data are available regarding the intrinsic membrane properties of CE amygdala neurons. Here, we characterized the physiological properties of CE medial (CE(M)) and CE lateral (CE(L)) amygdala neurons using whole cell recordings in brain slices maintained in vitro. Several classes of CE neurons were distinguished on the basis of their physiological properties. Most CE(M) cells (95%), here termed "late-firing neurons," displayed a marked voltage- and time-dependent outward rectification in the depolarizing direction. This phenomenon was associated with a conspicuous delay between the onset of depolarizing current pulses and the first action potential. During this delay, the membrane potential (V(m)) depolarized slowly, the steepness of this depolarizing ramp increasing as the prepulse V(m) was hyperpolarized from -60 to -90 mV. Low extracellular concentrations of 4-aminopyridine (30 microM) reversibly abolished the outward rectification and the delay to firing. Late-firing CE(M) neurons displayed a continuum of repetitive firing properties with cells generating single spikes at one pole and high-frequency (> or =90 Hz) spike bursts at the other. In contrast, only 56% of CE(L) cells displayed the late-firing behavior prevalent among CE(M) neurons. Moreover, these CE(L) neurons only generated single spikes in response to membrane depolarization. A second major class of CE(L) cells (38%) lacked the characteristic delay to firing observed in CE(M) cells, generated single spikes in response to membrane depolarization, and displayed various degrees of inward rectification in the hyperpolarizing direction. In both regions of the CE nucleus, two additional cell types were encountered infrequently (< or =6% of our samples). One type of neurons, termed "low-threshold bursting cells" had a behavior reminiscent of thalamocortical neurons. The second type of cells, called "fast-spiking cells," generated brief action potentials at high rates with little spike frequency adaptation in response to depolarizing current pulses. These findings indicate that the CE nucleus contains several types of neurons endowed with distinct physiological properties. Moreover, these various cell types are not distributed uniformly in the medial and lateral sector of the CE nucleus. This heterogeneity parallels anatomic data indicating that these subnuclei are part of different circuits.

4-Aminopyridine↗

PubMed1998

Functional and molecular differences between voltage-gated K+ channels of fast-spiking interneurons and pyramidal neurons of rat hippocampus.

We have examined gating and pharmacological characteristics of somatic K+ channels in fast-spiking interneurons and regularly spiking principal neurons of hippocampal slices. In nucleated patches isolated from basket cells of the dentate gyrus, a fast delayed rectifier K+ current component that was highly sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (half-maximal inhibitory concentrations <0.1 mM) predominated, contributing an average of 58% to the total K+ current in these cells. By contrast, in pyramidal neurons of the CA1 region a rapidly inactivating A-type K+ current component that was TEA-resistant prevailed, contributing 61% to the total K+ current. Both types of neurons also showed small amounts of the K+ current component mainly found in the other type of neuron and, in addition, a slow delayed rectifier K+ current component with intermediate properties (slow inactivation, intermediate sensitivity to TEA). Single-cell RT-PCR analysis of mRNA revealed that Kv3 (Kv3.1, Kv3.2) subunit transcripts were expressed in almost all (89%) of the interneurons but only in 17% of the pyramidal neurons. In contrast, Kv4 (Kv4.2, Kv4.3) subunit mRNAs were present in 87% of pyramidal neurons but only in 55% of interneurons. Selective block of fast delayed rectifier K+ channels, presumably assembled from Kv3 subunits, by 4-AP reduced substantially the action potential frequency in interneurons. These results indicate that the differential expression of Kv3 and Kv4 subunits shapes the action potential phenotypes of principal neurons and interneurons in the cortex.

4-Aminopyridine↗

PubMed1998

Multiple modulatory effects of dopamine on calcium channel kinetics in adult rat sensory neurons.

1. The aim of this research was to study the modulatory effects induced on high-voltage-activated (HVA) calcium channels and pharmacologically isolated subtypes through dopamine receptor activation. 2. The experiments were carried out on acutely isolated adult rat sensory neurons, recorded by means of the whole-cell patch-clamp technique. 3. At saturating concentrations dopamine was effective in inducing: (a) a voltage-dependent prolongation of activation kinetics, (b) a voltage-independent scaling down of the currents without any changes in activation and inactivation kinetics, and (c) an acceleration of inactivation kinetics, not affected by a positive conditioning prepulse. 4. These three inhibitory effects were observed on N- and P/Q-type currents, whereas only a voltage-independent scaling up and/or scaling down was observed on L-type current. 5. The inhibitory effects were sometimes observed in isolation in different neurons, but more frequently they were variously combined in the same cell. A correlation analysis of these effects shows no relationship between them, corroborating the conclusion that they are mechanistically distinct. 6. The existence of an inactivating effect accounts for the occurrence of a voltage-dependent inhibitory effect in some cells without an apparent slowing down of activation kinetics, since the increased inactivation may mask the slow component of the activation. 7. The multiple modulatory effects on calcium channels, even on pharmacologically separated N-, L- and P/Q-currents, suggest that pharmacological and functional classifications do not necessarily match completely. 8. The multiple modulatory effects on HVA calcium currents may play a prominent role both in controlling the integrative properties of neurons and in regulating output at a presynaptic level.

Animals↗

PubMed1998

GABA excites immature CA3 pyramidal cells through bicuculline-sensitive and -insensitive chloride-dependent receptors.

Intracellular and patch clamp recording techniques were used to investigate the role of GABA in immature CA3 hippocampal neurons. During the first postnatal week spontaneous GABA release was detected as spontaneous ongoing synaptic potentials (SPSPs) or giant depolarizing potentials (GDPs). GDPs were generated at regular intervals and regulated by ionotropic glutamate receptors (GluRs), whereas SPSPs occurred randomly and were unaffected by ionotropic GluRs. Both GDPs and SPSPs were positively modulated by metabotropic GluRs through cyclic AMP-dependent protein kinase. Moreover GABA controlled its own release through GABAA and GABAB receptors, probably localized on GABAergic nerve terminals. At this developmental stage, GABA depolarized CA3 pyramidal cells through two distinct classes of chloride-permeable receptors: bicuculline sensitive and insensitive, respectively. The bicuculline-insensitive responses were blocked by picrotoxin in a noncompetitive way. Whole-cell GABA currents, recorded in the presence of bicuculline, had a slower desensitization rate and faster recovery from desensitization. In excised outside-out patches, in the presence of bicuculline, GABA activated single-channel currents with conductances of 14, 22, and 31 pS. These values were similar to those obtained when GABA was applied in the absence of bicuculline. Interestingly, GABA responses obtained in the absence of bicuculline, were sensitive to the blocking effect of zinc, whereas bicuculline-resistant responses were almost unaffected by this divalent cation. Expression of different subunits in native receptors (particularly of the alpha and rho type) may account for the functional differences observed in the present experiments. Activation of bicuculline-insensitive receptors would strengthen and prolong the depolarizing action of GABA, thus favoring the entry of calcium through voltage-dependent calcium channels. This calcium signal may be essential in promoting stabilization of synaptic contacts during a critical period of postnatal development.

Animals↗

PubMed1997

Functional differences in Na+ channel gating between fast-spiking interneurones and principal neurones of rat hippocampus.

1. GABAergic interneurones differ from glutamatergic principal neurones in their ability to discharge high-frequency trains of action potentials without adaptation. To examine whether Na+ channel gating contributed to these differences, Na+ currents were recorded in nucleated patches from interneurones (dentate gyrus basket cells, BCs) and principal neurones (CA1 pyramidal cells, PCs) of rat hippocampal slices. 2. The voltage dependence of Na+ channel activation in BCs and PCs was similar. The slope factors of the activation curves, fitted with Boltzmann functions raised to the third power, were 11.5 and 11.8 mV, and the mid-point potentials were -25.1 and -23.9 mV, respectively. 3. Whereas the time course of Na+ channel activation (-30 to +40 mV) was similar, the deactivation kinetics (-100 to -40 mV) were faster in BCs than in PCs (tail current decay time constants, 0.13 and 0.20 ms, respectively, at -40 mV). 4. Na+ channels in BCs and PCs differed in the voltage dependence of inactivation. The slope factors of the steady-state inactivation curves fitted with Boltzmann functions were 6.7 and 10.7 mV, and the mid-point potentials were -58.3 and -62.9 mV, respectively. 5. The onset of Na+ channel inactivation at -55 mV was slower in BCs than in PCs; the inactivation time constants were 18.6 and 9.3 ms, respectively. At more positive potentials the differences in inactivation onset were smaller. 6. The time course of recovery of Na+ channels from inactivation induced by a 30 ms pulse was fast and mono-exponential (tau = 2.0 ms at -120 mV) in BCs, whereas it was slower and bi-exponential in PCs (tau 1 = 2.0 ms and tau 2 = 133 ms; amplitude contribution of the slow component, 15%). 7. We conclude that Na+ channels of BCs and PCs differ in gating properties that contribute to the characteristic action potential patterns of the two types of neurones.

Action Potentials↗

PubMed1997

Membrane stretch activates a potassium channel in pig articular chondrocytes.

Activity of stretch-activated potassium channels has been recorded in articular chondrocytes using patch-clamp technique. Pressure dependence is described by a sigmoidal function with a half-maximum effect at -20.5 mbar. Selectivity for potassium is demonstrated by agreement between the reversal potential measured at different [K+]o and the prediction of Nernst equation and by block of these channels by caesium.

Animals↗

PubMed1997

A large-conductance voltage-dependent potassium channel in cultured pig articular chondrocytes.

The patch-clamp techniques were used to study voltage-dependent potassium channels in cultured pig articular chondrocytes. A predominant single-channel conductance of 125 pS was found. These channels were reversibly blocked by tetraethylammonium. In cell-attached patches, transient increases in the channel activity were observed, and defined as a switching between low and high activity modes (LAM and HAM). Open-time distributions could be described with two kinetics components (in LAM and HAM) having similar time constants (fast tau1 and slow tau2). In HAM, the area of the slow component was larger. The mean burst length was significantly longer in HAM than in LAM. In both modes, the burst-length distributions were fitted with a sum of three exponentials. In LAM and HAM, the time constants tau1 and tau2 were indistinguishable from those of the open-time distributions. The slowest time constant, tau3, was strongly voltage dependent, and was significantly longer in HAM than in LAM. In both LAM and HAM, the ensemble currents were characterised by a rapid rising phase followed by fast and profound inactivation. The activation kinetics were similar, but the inactivation was faster in HAM. In the outside-out configuration no evidence for mode switching was found. The kinetics of the rising phase of the ensemble currents were also similar to those observed using the cell-attached configuration, but the channels did not inactivate. In the whole-cell configuration, the mode switching was not present. The inactivation time constant showed a large scattering, and was much slower than that measured in the cell-attached patch mode. These currents were blocked by tetraethylammonium and 4-aminopyridine. Our results indicate that intracellular factors are involved in controlling the mode switching and the kinetics of the inactivation of potassium channels in pig articular chondrocytes.

Animals↗

PubMed1997

Functionally distinct chloride-mediated GABA responses in rat cerebellar granule cells cultured in a low-potassium medium.

The patch-clamp technique was used to study whole cell currents evoked by gamma-aminobutyric acid (GABA) in rat cerebellar granule cells cultured in 5 mM potassium, a condition that favors the development of functional GABAergic synapses. GABA activated both high- and low-sensitivity receptors. The high-sensitivity receptor had an effective concentration producing half the maximum response (EC50) of 13 microM, whereas the low-sensitivity one had an EC50 of 255 microM. The GABAA receptor agonist isoguvacine activated only the high-sensitivity receptor with an EC50 of 16 microM. When GABA was applied during the desensitized phase of the response elicited by a saturating concentration of isoguvacine, it was still able to induce a small response, whereas when isoguvacine was applied during the desensitizing phase of GABA-evoked current no response was detected. GABA responses were highly heterogeneous regarding their sensitivity to bicuculline. In a small number of cells (3 of 25), bicuculline (10 microM) completely abolished GABA-evoked currents. In the majority of the neurons (22 of 25) the blocking effect of bicuculline (100 microM) was 64 +/- 4% (mean +/- SE). The bicuculline-resistant component was abolished by picrotoxin (100 microM). In bicuculline, the dose-response curve for GABA was fitted with a sigmoidal curve with an EC50 value of 209 microM. These data indicate that functional new GABA receptor types with unusual pharmacology could be switched on by conditions that maintain cells in their undifferentiated state.

Animals↗

PubMed1996

The calcineurin inhibitor cyclosporin A-cyclophilin A complex reduces desensitization of GABAA-mediated responses in acutely dissociated rat hippocampal neurons.

The effects of the selective inhibitor of calcineurin, cyclosporin A-cyclophilin A (CC) complex on the desensitization kinetics of GABAA receptors was studied in acutely dissociated hippocampal neurons, using the patch clamp technique in the whole cell configuration. In control conditions, the decay of GABA-evoked current could be fitted by a biexponential function having time constants of 0.65 +/- 0.24 s and 3.75 +/- 2 s. The plateau to peak ratio was 0.087 +/- 0.034. Recovery from desensitization was obtained in more than 2 min. In cells dialyzed with the CC complex, the decay of the currents could be fitted with the sum of two exponentials having time constants similar to controls (0.81 +/- 0.47 s and 3.62 +/- 2.1 s), but the percentage of the fast component was smaller. The plateau to peak ratio was significantly larger than control (0.185 +/- 0.07). With CC complex, recovery from desensitization was completed in almost 30 s. The cyclosporin A derivative PSC 833, which does not inhibit calcineurin, did not affect desensitization kinetics. These results suggest that phosphatase 2B regulates desensitization of GABAA receptors.

Animals↗

PubMed1996

Zinc modulation of bicuculline-sensitive and -insensitive GABA receptors in the developing rat hippocampus.

Intracellular recordings were used to study the effects of zinc on the bicuculline-sensitive and -insensitive responses evoked by GABA in CA3 rat hippocampal neurons in slices obtained from postnatal day (P) 0 to P8. In the absence of bicuculline, zinc inhibited GABA-induced responses in a concentration-dependent manner. This effect was developmentally regulated, being maximal (50%) between P0 and P5 and then declining to 30% after P5. In the presence of bicuculline, GABA-resistant responses were potentiated in 49% of cases, depressed in 38% and not affected in 13%. The period of maximum potentiation between P0 and P2 coincided with that of maximum expression of the bicuculline-resistant receptors. The effects of zinc were also studied using the whole-cell and outside-out configuration of the patch-clamp technique on bicuculline-sensitive and -insensitive GABA-induced currents elicited in isolated cells acutely dissociated from the same slices as those used for intracellular recordings. At a holding potential of -50 mV in symmetrical chloride solutions, GABA (50 and 100 microM) activated whole-cell inward currents which were reversibly blocked by zinc. The EC50 values for the blocking effect of zinc on currents evoked by 50 and 100 microM GABA were 6.6 nM and 5.8 microM respectively. In the presence of bicuculline (100 microM), zinc potentiated the residual responses to GABA; the response curve was bell-shaped with a peak at 1 microM. When the response to GABA was completely abolished by bicuculline, zinc (1 microM) was often able to restore it. In the presence of bicuculline, however, zinc was not able to restore the response to isoguvacine. In two excised outside-out patches, zinc (1 microM) increased the activity of opening of bicuculline-resistant GABA-evoked single channel currents (Np) from 1 to 1.87 and from 0.25 to 0.42 respectively, without changing single-channel conductance. These data suggest that down- or up-regulation of bicuculline-sensitive or -insensitive GABA receptors may be functionally important in regulating synaptic activity during development.

Animals↗

PubMed1995

Calcium influx in rat thalamic relay neurons through voltage-dependent calcium channels is inhibited by enkephalin.

High and low voltage-activated, transient (HVA and LVA,T) Ca2+ currents are crucial in determining the characteristic thalamic firing pattern, during the oscillatory mode. The modulatory effects induced by D-ala2-D-leu5-enkephalin (DADLE) on voltage-dependent Ca2+ channels have been investigated on acutely dissociated neurons from rat ventro-basal (VB) thalamus, by means of whole cell patch-clamp technique. DADLE (400 nM) reduced HVA Ca2+ channel currents in 37 out of 44 cells tested (-53 +/- 5.3% to 0 mV test potential, n = 24,). In 50% of the cases DADLE induced an effect which was persistent at all the potentials tested, i.e. a voltage-independent one. In the remaining neurons, the inhibition partially or totally disappeared on the currents evoked at the highest potentials. DADLE was also able to inhibit LVA Ca2+ channels (-40% in five out of 12 cells). In conclusion, thalamic relay neurons present opioid receptors negatively coupled to both HVA and LVA Ca2+ channels. The presence of two inhibitory effects of DADLE on the total HVA Ca2+ channels has been observed, and they are distinguishable on the basis of their sensitivity to voltage. It is suggested that Ca2+ current modulation may play a role in the production and tuning of the rhythmic burst discharge in these neurons.

Animals↗