Biomedical subjects

D A Prince

Publications and source records attributed to D A Prince.

At least 73 records · Page 4Linked to original sources

PubMed1991

A fast transient potassium current in thalamic relay neurons: kinetics of activation and inactivation.

1. Whole-cell voltage-clamp techniques were used to record K+ currents in relay neurons (RNs) that had been acutely isolated from rat thalamic ventrobasal complex and maintained at 23 degrees C in vitro. Tetrodoxin (TTX; 0.5 microM) was used to block Na+ currents, and reduced extracellular levels of Ca2+ (1 mM) were used to minimize contributions from Ca2+ current (ICa). 2. In RNs, depolarizing commands activate K+ currents characterized by a substantial rapidly inactivating (time constant approximately 20 ms) component, the features of which correspond to those of the transient K+ current (IA) in other preparations, and by a smaller, more slowly activating K+ current, "IK". IA was reversibly blocked by 4-aminopyridine (4-AP, 5 mM), and the reversal potential varied with [K+]o as predicted by the Nernst equation. 3. IA was relatively insensitive to blockade by tetraethylammonium [TEA; 50%-inhibitory concentration (IC50) much much greater than 20 mM]; however, two components of IK were blocked with IC50S of 30 microM and 3 mM. Because 20 mM TEA blocked 90% of the sustained current while reducing IA by less than 10%, this concentration was routinely used in experiments in which IA was isolated and characterized. To further minimize contamination by other conductances, 4-AP was added to TEA-containing solutions and the 4-AP-sensitive current was obtained by subtraction. 4. Voltage-dependent steady-state inactivation of peak IA was described by a Boltzman function with a slope factor (k) of -6.5 and half-inactivation (V1/2) occurring at -75 mV. Activation of IA was characterized by a Boltzman curve with V1/2 = -35 mV and k = 10.8. 5. IA activation and inactivation kinetics were best fitted by the Hodgkin-Huxley m4h formalism. The rate of activation was voltage dependent, with tau m decreasing from 2.3 ms at -40 mV to 0.5 ms at +50 mV. Inactivation was relatively voltage independent and nonexponential. The rate of inactivation was described by two exponential decay processes with time constants (tau h1 and tau h2) of 20 and 60 ms. Both components were steady-state inactivated with similar voltage dependence. 6. Temperature increases within the range of 23-35 degrees C caused IA activation and inactivation rates to become faster, with temperature coefficient (Q10) values averaging 2.8. IA amplitude also increased as a function of temperature, albeit with a somewhat lower Q10 of 1.6. 7. Several voltage-dependent properties of IA closely resemble those of the transient inward Ca2+ current, IT. (ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗

PubMed1991

Slow inactivation of a TEA-sensitive K current in acutely isolated rat thalamic relay neurons.

1. Voltage-gated K currents were studied in relay neurons (RNs) acutely isolated from somatosensory (VB) thalamus of 7- to 14-day-old rats. In addition to a rapidly activated, transient outward current, IA, depolarizations activated slower K+ currents, which were isolated through the use of appropriate ionic and pharmacological conditions and measured via whole-cell voltage-clamp. 2. At least two slow components of outward current were observed, both of which were sensitive to changes in [K+]o, as expected for K conductances. The first, IK1, had an amplitude that was insensitive to holding potential and a relatively small conductance of 150 pS/pF. It was blocked by submillimolar levels of tetraethylammonium [TEA, 50%-inhibitory concentration (IC50 = 30 microM)] and 4-aminopyridine (4-AP, 40 microM). In the absence of intracellular Ca2+ buffering, the amplitude of IK1 was both larger and dependent on holding potential, as expected for a Ca(2+)-dependent current. Replacement of [Ca2+]o by Co2+ reduced IK1, although the addition of Cd2+ to Ca(2+)-containing solutions had no effect. 3. The second component, IK2, had a normalized conductance of 2.0 nS/pF and was blocked by millimolar concentrations of TEA (IC50 = 4 mM) but not by 4AP. The kinetics of IK2 were analogous to (but much slower than) those of IA in that both currents displayed voltage-dependent activation and voltage-independent inactivation. IK2 was not reduced by the addition of Cd2+ to Ca(2+)-containing solutions or by replacement of Ca2+ by Co2+. 4. IK2 had a more depolarized activation threshold than IA and attained peak amplitude with a latency of approximately 100 ms at room temperature. IK2 decay was nonexponential and could be described as the sum of two components with time constants (tau) near 1 and 10 s. 5. IK2 was one-half steady-state inactivated at a membrane potential of -63 mV, near the normal resting potential for these cells. The slope factor of the Boltzman function describing steady-state inactivation was 13 mV-1, which indicates that IK2 varies in availability across a broad voltage range between -100 and -20 mV. 6. Activation kinetics of IK2 were voltage dependent, with peak latency shifting from 300 to 50 ms in the voltage range -50 to +30 mV. Deinactivation and deactivation were also voltage dependent, in contrast to inactivation, which showed little dependence on membrane potential. Increase in temperature sped the kinetics of IK2, with temperature coefficient (Q10) values near 3 for activation and inactivation. Heating increased the amplitude of IK2 with a Q10 value near 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Control of NMDA receptor-mediated activity by GABAergic mechanisms in mature and developing rat neocortex.

The effects of diazepam and low concentrations of bicuculline methiodide (BMI) on the expression of long-latency N-methyl-D-aspartate (NMDA) receptor-mediated activity was studied in supragranular layers of juvenile (14-18 days old) and adult rat (greater than or equal to 28 days) primary somatosensory cortex. In juvenile slices, orthodromic stimulation of layer VI/white matter evoked a long-lasting oscillatory field potential response which could be blocked by the NMDA receptor antagonist D(-)-2-amino-5-phosphonovaleric acid (D-APV) and by diazepam. Similar D-APV-sensitive responses could be observed in adult slices when the GABAergic system was slightly suppressed by adding low doses of BMI to the bathing solution. Our findings indicate that a small decrease in the efficacy of the inhibitory system, whether caused by developmental events or by processes that modulate inhibitory electrogenesis, can lead to NMDA receptor-mediated synchronized afterdischarges, which might play an important role in the functional maturation of the neocortex and in susceptibility to epileptogenesis.

2-Amino-5-phosphonovalerate↗

PubMed1990

Burst generating and regular spiking layer 5 pyramidal neurons of rat neocortex have different morphological features.

Intracellular recordings were obtained from pyramidal neurons in layer 5 of rat somatosensory and visual cortical slices maintained in vitro. When directly depolarized, one subclass of pyramidal neurons had the capacity to generate intrinsic burst discharges and another generated regular trains of single spikes. Burst responses were triggered in an all-or-none manner from depolarizing afterpotentials in most bursting neurons. Regular spiking cells responded to electrical stimulation of ascending afferents with a typical EPSP-IPSP sequence, whereas IPSPs were hard to detect in bursting cells. Orthodromic activation of the latter evoked a prominent voltage-dependent depolarization that could trigger a burst response. Intracellularly labelled bursting and regular spiking cells were located in layer 5b, but had distinctly different morphologies. Bursting neurons had a large pyramidal soma, a gradually emerging apical dendrite, and an extensive apical and basal dendritic tree. Their axonal collateral arborization was predominantly limited to layers 5/6. In contrast, regular spiking cells had a more rounded soma with abruptly emerging apical dendrite, a smaller dendritic arborization, and 2 to 8 ascending axonal collaterals that arborized widely in the supragranular layers. Both bursting and regular spiking cells had main axons that entered the subcortical white matter. These data show that some subgroups of pyramidal neurons within the deeper parts of layer 5 of rat cortex are morphologically and physiologically distinct and have different intracortical connections. Bursting cells presumably function to amplify and synchronize cortical outputs, whereas regular spiking output neurons provide excitatory feedback to neurons at all cortical levels and receive a more effective orthodromic inhibitory input. These data support the hypothesis that differences in gross neuronal structure, perhaps even the subtle differences that distinguish subclasses of neurons in a given lamina, are predictive of underlying differences in the type and distribution of ion channels in the nerve cell membrane and connections of cells within the cortical circuit.

Animals↗

PubMed1990

Transient expression of polysynaptic NMDA receptor-mediated activity during neocortical development.

During a restricted period of early postnatal development, rat neocortical neurons receive a powerful N-methyl-D-aspartate (NMDA) receptor-mediated synaptic input of variable onset latency and duration. These large-amplitude excitatory postsynaptic potentials are especially pronounced in supragranular layers and are generated by activities in polysynaptic circuits. Their occurrence in cortical slices from juvenile (postnatal (P) days 11-20), but not neonatal (P5-10) or adult (greater than or equal to P28) animals, appears to be in part a consequence of the relative immaturity of gamma-aminobutyric acid (GABA)-mediated inhibition, at a time when the requisite functional excitatory circuitry has been established. The transient manifestation of strong NMDA receptor-mediated potentials coincides temporally with a 'developmental window' within which there is enhanced sensitivity for epileptogenesis and for induction of long-term synaptic modifications in rat cortex.

2-Amino-5-phosphonovalerate↗

PubMed1990

Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: calcium current reduction.

1. Succinimide derivatives can be either convulsant (tetramethylsuccinimide (TMS)), or anticonvulsant (ethosuximide (ES); alpha-methyl-alpha-phenylsuccinimide (MPS)). ES, an anticonvulsant succinimide, has previously been shown to block calcium currents of thalamic neurones, while the convulsant succinimide TMS blocks gamma-aminobutyric acid (GABA) responses in a similar fashion to the convulsant pentylenetetrazol (PTZ). 2. Using voltage-clamp techniques, we analysed the effects of the anticonvulsant succinimides ES and MPS and the convulsants TMS and PTZ on calcium currents of acutely isolated thalamic relay neurones of the rat. 3. MPS and ES reduced low-threshold calcium current (LTCC) in a voltage-dependent manner, without affecting steady-state inactivation. MPS was less potent than ES (IC50 of 1100 vs 200 microM) but greater in efficacy (100% maximal reduction vs 40% for ES). 4. PTZ had no effect on calcium currents, and TMS only reduced LTCC at very high concentrations, and did not occlude MPS effects when applied concurrently. 5. These results, which demonstrate that anticonvulsant, but not convulsant, succinimides block LTCC, provide additional support for the hypothesis that LTCC reduction is a mechanism of action of the anticonvulsant succinimides related to their effects in petit mal epilepsy.

Animals↗

PubMed1990

Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: GABA current blockade.

1. Currents evoked by applications of gamma-aminobutyric acid (GABA) to acutely dissociated thalamic neurones were analysed by voltage-clamp techniques, and the effects of the anticonvulsant succinimides ethosuximide (ES) and alpha-methyl-alpha-phenylsuccinimide (MPS) and the convulsants tetramethylsuccinimide (TMS), picrotoxin, pentylenetetrazol (PTZ), and bicuculline methiodide were assessed. 2. TMS (1 microM-10 microM) reduced responses to iontophoretically applied GABA, as did picrotoxin (0.1-100 microM), PTZ (1-100 mM) and bicuculline (1-100 microM). 3. ES, in high concentrations (1-10 mM), reduced GABA responses to a lesser extent, and also occluded the reductions in GABA-evoked currents produced by TMS, picrotoxin, and PTZ. ES did not occlude the effects of bicuculline on GABA responses. Therefore, we propose that ES acts as a partial agonist at the picrotoxin GABA-blocking receptor. 4. MPS had no effect on GABA responses (at a concentration of 1 mM), and, like ES, occluded the GABA-blocking actions of TMS, apparently acting as a full antagonist. 5. The anticonvulsant actions of ES and MPS against TMS and PTZ-induced seizures may thus involve two independent mechanisms: (1) the occlusion of TMS and PTZ GABA-blocking effects; and (2) the previously described specific effect of ES and MPS on low-threshold calcium current of thalamic neurones. The latter cellular mechanism may be more closely related to petit mal anticonvulsant activity.

Animals↗

PubMed1989

Specific petit mal anticonvulsants reduce calcium currents in thalamic neurons.

Low-threshold calcium current (LTCC) in thalamic neurons is important in generation of normal thalamocortical rhythms, and may be involved in the genesis of abnormal activities such as spike-wave discharges that characterize petit mal epilepsy. Ethosuximide and dimethadione, anticonvulsants effective in petit mal, reduced the LTCC when applied to thalamic neurons at clinically relevant concentrations. Therapeutic concentrations of phenytoin and carbamazepine, drugs ineffective in the control of petit mal, had minimal effects on calcium conductances. Reduction in LTCC may be an important mechanism of action by which specific petit mal anticonvulsants depress spike-wave activity.

Action Potentials↗

PubMed1989

Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons.

The mechanism by which ethosuximide reduces thalamic low-threshold calcium current (LTCC) was analyzed using voltage-clamp techniques in acutely isolated ventrobasal complex neurons from rats and guinea pigs. The ethosuximide-induced reduction of LTCC was voltage dependent: it was most pronounced at more-hyperpolarized potentials and did not affect the time course of activation or inactivation of the current. Ethosuximide reduced LTCC without altering the voltage dependence of steady-state inactivation or the time course of recovery from inactivation. Dimethadione reduced LTCC by a similar mechanism, while valproic acid had no effect on LTCC. We conclude that ethosuximide reduction of LTCC in thalamic neurons is consistent with a reduction in the number of available LTCC channels or in the single LTCC channel conductance, perhaps indicating a direct channel-blocking action of this drug. Given the importance of LTCC in thalamic oscillatory behavior, a reduction in this current by ethosuximide would be a mechanism of action compatible with the known anticonvulsant effects of this drug in typical absence seizures.

Animals↗

PubMed1989

Sodium channels in dendrites of rat cortical pyramidal neurons.

The voltage-dependent properties that have been directly demonstrated in Purkinje cell and hippocampal pyramidal cell dendrites play an important role in the integrative capacities of these neurons. By contrast, the properties of neocortical pyramidal cell dendritic membranes have been more difficult to assess. Active dendritic conductances near sites of synaptic input would have an important effect on the input-output characteristics of these neurons. In the experiments reported here, we obtained direct evidence for the existence of voltage-dependent Na+ channels on the dendrites of neocortical neurons by using cell-attached patch and whole cell recordings from acutely isolated rat neocortical pyramidal cells. The qualitative and quantitative properties of dendritic and somatic currents were indistinguishable. Insofar as Na+ currents are concerned, the soma and primary apical dendrite can be considered as one relatively uniform compartment. Similar dendritic Na+ currents on dendrites in mature neurons would play an important role in determining the integrative properties of these cortical units.

Animals↗

PubMed1989

Frequency-dependent depression of inhibition in guinea-pig neocortex in vitro by GABAB receptor feed-back on GABA release.

1. The mechanisms involved in the lability of inhibition at higher frequencies of stimulation were investigated in the guinea-pig in vitro neocortical slice preparation by intracellular recording techniques. We attempted to test the possibility of a feedback depression of GABA on subsequent release. 2. At resting membrane potential (Em, -75.8 +/- 5.2 mV) stimulation of either the pial surface or subcortical white matter evoked a sequence of depolarizing and hyperpolarizing synaptic components in most neurones. An early hyperpolarizing component (IPSPA) was usually only obvious as a pronounced termination of the EPSP, followed by a later hyperpolarizing event (IPSPB). Current-voltage relationships revealed two different conductances of about 200 and 20 nS and reversal potentials of -73.0 +/- 4.4 and -88.6 +/- 6.1 mV for the early and late component, respectively. 3. The conductances of IPSPA and IPSPB were fairly stable at a stimulus frequency of 0.1 Hz. At frequencies between 0.5 and 2 Hz both IPSPs were attenuated with the second stimulus and after about five stimuli a steady state was reached. Concomitantly IPSPs were shortened. The average decrease in synaptic conductance between 0.1 and 1 Hz was 80% for the IPSPA and 60% for the IPSPB. At these frequencies the reversal potentials decreased by 5 and 2 mV, respectively; Em and input resistance (Rin) were not consistently affected. 4. The amplitudes of field potentials, action potentials and EPSPs of pyramidal cells were attenuated less than 10% at stimulus frequencies up to 1 Hz, suggesting that alterations in local circuits between the stimulation site and excitatory input onto inhibitory interneurones may play only a minor role in the frequency-dependent decay of IPSPs. 5. Localized application of GABA produced multiphasic responses. With low concentrations and application near the soma an early hyperpolarization prevailed followed by a depolarizing late component. Brief application of GABA at low frequencies induced constant responses; at higher frequencies, the responses sometimes declined. The current-voltage relationships of the two GABA responses were similar to each other and to the early IPSP. An apparently fivefold higher conductance was estimated at lower Ems, suggesting that the GABA response had a voltage sensitivity. The slope conductance of IPSPs was decreased by up to 50% for tens of seconds after postsynaptically detectable effects of GABA had dissipated. 6. Application of the GABA uptake inhibitor nipecotic acid (50-500 microM) reduced the conductance of both components of orthodromically evoked inhibition and shortened the IPSP at low frequencies, but had no additional effects at higher stimulation rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Calcium currents in rat thalamocortical relay neurones: kinetic properties of the transient, low-threshold current.

1. Calcium currents were recorded with whole-cell voltage-clamp procedures in relay neurones of the rat thalamus which had been acutely isolated by an enzymatic dissociation procedure. 2. Low-threshold and high-threshold Ca2+ currents were elicited by depolarizing voltage steps from holding potentials more negative than -60 mV. A transient current, analogous to the T-current in sensory neurones, was activated at low threshold near -65 mV and was completely inactivating at command steps up to -35 mV. Voltage steps to more depolarized levels activated a high-threshold current that inactivated slowly and incompletely during a 200 ms step depolarization. 3. The high-threshold current contained both non-inactivating and slowly inactivating components which were insensitive and sensitive to holding potential, respectively. 4. A 'T-type' current was prominent in relay neurones, in both absolute terms (350 pA peak current average) and in relation to high-threshold currents. The average ratio of maximum transient to maximum sustained current was greater than 2. 5. T-current could be modelled in a manner analogous to that employed for the fast Na+ current underlying action potential generation, using the m3h format. The rate of activation of T-current was voltage dependent, with a time constant (tau m) varying between 8 and 2 ms at command potentials of -60 to -10 mV at 23 degrees C. The rate of inactivation was also voltage dependent, and the time constant tau h varied between 50 and 20 ms over the same voltage range. With command potentials more positive than -35 mV, the inactivation of Ca2+ current could no longer be fitted by a single exponential. 6. Steady-state inactivation of T-current could be well fitted by a Boltzman equation with slope factor of 6.3 and half-inactivated voltage of -83.5 mV. 7. Recovery from inactivation of T-current was not exponential. The major component of recovery (70-80% of total) was not very voltage sensitive at potentials more negative than -90 mV, with tau r of 251 ms at -92 mV and 23 degrees C, compared to 225 ms at -112 mV. A smaller, voltage-sensitive component accounted for the remainder of recovery. 8. All kinetic properties, including rates of activation, inactivation, and recovery from inactivation, as well as the amplitude of T-current, were temperature sensitive with Q10 (temperature coefficient) values of greater than 2.5.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Outward chloride/cation co-transport in mammalian cortical neurons.

The mechanism underlying outward chloride transport in guinea pig cingulate cortical neurons of in vitro slices was characterized with respect to its pharmacological antagonists and anion selectivity, and the nature of other ion movements coupled to Cl- transport. Changes in intracellular Cl- concentration, following iontophoresis of Cl- from KCl-filled intracellular recording electrodes, were estimated from changes in the amplitude of GABAergic, Cl(-)-mediated inhibitory postsynaptic potentials (IPSPs). The rate of outward Cl- transport was found to be reduced by bumetanide but not by SITS. SCN-, but not NO3-, was found to be actively transported. Increasing the extracellular K+ concentration ([K+]o) from 2.5 to 10 mM was found to inhibit Cl- extrusion. These data suggest that active Cl- extrusion from mammalian cortical neurons is mediated by an outwardly directed chloride/cation cotransport mechanism. Inhibition of this process by elevated [K+]o may be important in epilepsy.

Animals↗

PubMed1988

Dextromethorphan, a common antitussive, reduces kindled amygdala seizures in the rat.

Dextromethorphan (DM), a non-prescription antitussive, has anticonvulsant properties and antagonizes N-methyl-D-aspartate (NMDA) receptor-mediated responses in rat spinal and cortical neurons. The effects of daily intraperitoneal injections of DM on amygdala-kindled seizures were examined. DM was found both to prevent the development of full kindling in rats and to decrease seizure intensity in previously fully kindled animals. The findings of this study, combined with the ready availability of DM and its apparent safety in antitussive doses suggest that clinical testing of this drug as an anticonvulsant is warranted.

Amygdala↗

PubMed1988

Dextromethorphan protects against cerebral infarction in a rat model of hypoxia-ischemia.

We assessed the cerebral protective effects of the noncompetitive N-methyl-D-aspartate antagonist dextromethorphan (DM; 10-35 mg/kg i.p.) in 8-day-old rats that were subjected to brain hypoxia-ischemia by tying one carotid artery and placing them in 8% O2-92% N2 for 2 h. Light microscopic examination of brains perfused one week after the insult revealed that all control animals developed a frank infarction with cavitation and brain shrinkage in the middle cerebral artery territory. There was a highly significant decrease in the incidence of frank infarction in DM-pre-treated pups vs saline-treated littermates, although there was no clear relationship between drug dose and the degree of brain protection. DM and its active metabolite dextrorphan may prove to be clinically useful in protecting against hypoxia-ischemia.

Animals↗

PubMed1988

Dextrorphan and dextromethorphan, common antitussives, are antiepileptic and antagonize N-methyl-D-aspartate in brain slices.

The antitussive, dextromethorphan (DM), and its metabolite, dextrorphan (DX), were evaluated for antiepileptic properties in vitro. Interictal bursts and prolonged ictal epileptiform afterdischarges, induced by perfusion of guinea pig neocortical brain slices with Mg2+-free solution, were blocked by DX (1-250 microM) or DM (100 microM). Intracellular records showed that these agents blocked N-methyl-D-aspartate (NMDA)-induced depolarizations without altering intrinsic membrane properties. DX blocked NMDA but not quisqualate-evoked multi-unit excitatory responses. DM is a widely available, orally effective drug with low toxicity in antitussive doses, which has antiepileptic and NMDA-antagonist properties in vitro. Its toxicity and effectiveness as an anticonvulsant should be expeditiously examined in clinical trials.

2-Amino-5-phosphonovalerate↗

PubMed1988

Developmental changes in Na+ conductances in rat neocortical neurons: appearance of a slowly inactivating component.

1. Na+ conductances have been characterized in rat neocortical neurons from the sensorimotor area. Neurons were obtained by acute dissociation from animals at developmental stages from embryonic day 16 (E16) to postnatal day 50 (P50) to quantify any developmental changes in the kinetic properties of the Na+ conductance. 2. Neurons were divided into two classes, based on morphology, to determine whether there are any cell-type specific differences in Na+ conductances that contribute to the different action potential morphologies seen in current-clamp recordings in vitro. 3. Upon isolation, neurons were voltage clamped using the whole-cell variation of the patch-clamp technology. Both cell types, pyramidal and nonpyramidal, demonstrate large increases in Na+ current density during this developmental period (E16-P50). Normalized conductances were near 10 pS/micron2 in neurons from embryonic animals, and increased 6- to 10-fold during the first 2 wk postnatal. The final conductance reached in pyramidal neurons was higher than in non-pyramidal neurons. 4. We found no differences between the two cell types, pyramidal and nonpyramidal, in the voltage dependence of activation, inactivation kinetics, voltage dependence of steady-state inactivation, and recovery from inactivation. 5. The time course of Na+ current in immature neurons were fit with classical Hodgkin-Huxley kinetics. However, in more mature neurons the kinetics of inactivation became more complicated such that two decay components were required to obtain good fit. The slowly decaying component had a time course 5 to 10 times slower than the fast component. 6. Several procedures were used to reduce the magnitude of Na+ conductance in mature neurons to ensure graded, voltage-dependent inward currents. These included reduced extracellular [Na+], submaximal tetrodotoxin concentrations, and reduced holding potential. Under each of these conditions we were able to verify the observation that Na+ current inactivation occurs with two exponentials. 7. Single-channel Na+ currents were obtained from cell-attached patches. The membrane density of active Na+ channels increases with development, and ensemble averages from mature neurons demonstrated two inactivation processes. The slow inactivation process was accounted for by long-latency single-channel openings of the same amplitude as the short-latency openings. 8. We conclude that there are no kinetic differences in the Na+ channels between cell types. Differences in action potentials are then not explained by differences in Na+ current kinetics, but might be partially explained by the different densities.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Noradrenergic modulation of firing pattern in guinea pig and cat thalamic neurons, in vitro.

1. The electrophysiological actions of norepinephrine (NE) in the guinea pig and cat thalamus were investigated using intracellular recordings from neurons of in vitro thalamic slices. 2. Application of NE to neurons of the lateral and medial geniculate nuclei, nucleus reticularis, anteroventral nucleus, and the parataenial (PT) nucleus resulted in a slow depolarization associated with a 2- to 15-nS decrease in input conductance and an increase in the slow membrane time constant from an average of 27.7 to 37.7 ms. The slow depolarization was not abolished by blockade of synaptic transmission, indicating that it was a direct (postsynaptic) effect. 3. The reversal potential of the NE-induced slow depolarization varied as a Nernstian function of extracellular potassium concentration ([K]o), indicating that it is due to a decrease in potassium conductance. This conclusion was supported by the finding that the amplitude of the NE-evoked depolarization was affected by changes in [K]o between 0.5 and 5.0 mM as expected for a K-mediated response. 4. Neurons of the PT nucleus displayed unusually large afterhyperpolarizations (AHPs) in comparison to cells in other thalamic nuclei. NE application to PT neurons caused not only a marked slow depolarization and decreased conductance, but also selectively reduced the slow AHP. 5. The NE-induced slow depolarization effectively suppressed burst firing and promoted the occurrence of single spike activity. NE-induced reduction of the slow AHP in PT neurons was accompanied by a decrease in spike frequency accommodation and the emergence of a slow afterdepolarization. 6. We suggest that through these electrophysiological actions, NE can effectively inhibit the generation of thalamocortical rhythms and greatly facilitate the faithful transfer of information through the thalamus to the cerebral cortex.

Animals↗