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F F Weight

Publications and source records attributed to F F Weight.

At least 73 records · Page 4Linked to original sources
PubMed1989

Ethanol inhibits NMDA-activated ion current in hippocampal neurons.

The ion current induced by the glutamate receptor agonist N-methyl-D-aspartate (NMDA) in voltage-clamped hippocampal neurons was inhibited by ethanol (EtOH). Inhibition increased in a concentration-dependent manner over the range 5 to 50 mM, a range that also produces intoxication. The amplitude of the NMDA-activated current was reduced 61 percent by 50 mM EtOH; in contrast, this concentration of EtOH reduced the amplitude of current activated by the glutamate receptor agonists kainate and quisqualate by only 18 and 15 percent, respectively. The potency for inhibition of the NMDA-activated current by several alcohols is linearly related to their intoxicating potency, suggesting that alcohol-induced inhibition of responses to NMDA receptor activation may contribute to the neural and cognitive impairments associated with intoxication.

1-Butanol↗
PubMed1989

Transient low-threshold Ca2+ current triggers burst firing through an afterdepolarizing potential in an adult mammalian neuron.

In a variety of mammalian neurons, a brief depolarization generates an afterdepolarizing potential that triggers the firing of a short series or burst of action potentials. Although such burst firing is thought to contribute to the processing of neural information, the ionic currents that underlie this phenomenon have not been established. In whole-cell patch-clamp experiments on dorsal root ganglion neurons, we have found that the current that underlies this type of burst firing is a transient low-threshold (T-type) Ca2+ current. The data suggest that the T-type Ca2+ current may play an important role in the processing of information in the nervous system by virtue of its ability to elicit burst firing in neurons.

Action Potentials↗
PubMed1988

Glutamate induces a depolarization of adult rat dorsal root ganglion neurons that is mediated predominantly by NMDA receptors.

The effects of glutamate, glutamate receptor agonists and substances that affect glutamate responses were studied, using the whole-cell patch-clamp technique, on neurons isolated from adult rat dorsal root ganglia. In current-clamp, glutamate (100 microM) or the excitatory amino acid receptor agonist N-methyl-D-aspartate (NMDA; 10 or 100 microM) induced membrane depolarization. Under voltage-clamp, these compounds induced an inward current that was voltage-dependent in the presence of Mg2+. The NMDA-induced current was inhibited by the NMDA receptor antagonist D,L-2-amino-5-phosphono-valerate (APV; 100 microM), and potentiated by 100 nM glycine. Few neurons responded to the receptor agonists kainate (100 microM), or quisqualate (1-10 microM). These observations suggest that glutamate-induced depolarization of primary sensory neurons is mediated predominantly by NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1988

Membrane currents activated in acutely dissociated rat pineal cells during the circadian cycle.

Whole-cell patch-clamp recordings were performed in cells acutely dissociated from adult rat pineal glands in order to determine possible long lasting influences of the circadian rhythm upon voltage-activated membrane currents. Cells were dissociated either during the light or dark period. From a holding potential of -50 mV, pineal cells bathed in a normal solution responded to depolarizing potentials positive to -20 mV with a slowly rising sustained outward current. From a holding potential of -100 mV, a transient outward current was activated with command potentials positive to -50 mV. This current reached a peak within 15 ms and had a significant decay over 160 ms. In most of the cells, inward currents were not observed and no significant differences were found between the properties of the outward currents in cells dissociated during the light or dark period. This suggests that the previously reported circadian activity in the rat pineal gland is not associated with inward current or with long lasting changes in the voltage-activated membrane currents.

Animals↗
PubMed1988

Pharmacological studies in frog sympathetic ganglion: support for the cholinergic monosynaptic hypothesis for slow IPSP mediation.

The slow inhibitory postsynaptic potential (slow IPSP), the slow excitatory postsynaptic potential (slow EPSP), the late slow excitatory postsynaptic potential (late slow EPSP), and the fast excitatory postsynaptic potential/compound action potential (fast EPSP) were recorded from the 9th or 10th paravertebral sympathetic ganglia of bullfrogs (and some Rana pipiens frogs) by the sucrose-gap technique. The adrenergic antagonists phentolamine, dihydroergotamine and propranolol did not show any antagonistic effect on the slow IPSP when used at concentrations of up to 10, 100 and 10 microM, respectively. U-0521 (3',4'-dihydroxy-2-methylpropriophenone, 50 micrograms/ml), a specific inhibitor of catechol-O-methyltransferase, did not show any potentiating effect on the slow IPSP. The cholinesterase inhibitor neostigmine (0.5-1 microM) induced a large increase in the duration and amplitude of slow IPSP. When phentolamine and propranolol at concentrations greater than 10 microM were used the slow IPSP (and all other synaptic potentials) were non-specifically reduced in amplitude by these drugs. The results reported in this paper do not lend any support to the hypothesis that the slow IPSP in frog sympathetic ganglia is mediated by an adrenergic interneuron. The results are consistent with the proposal that the slow IPSP in this ganglion is mediated by a direct action of acetylcholine released from cholinergic preganglionic fibers.

Action Potentials↗
PubMed1988

Acute ethanol administration selectively alters localized cerebral glucose metabolism.

The effects of acute ethanol administration on glucose utilization in the CNS of rat were studied using the 2-deoxyglucose technique. Cerebral glucose utilization was determined for 53 brain regions at peak and descending blood ethanol concentrations averaging 14, 26 and 66 mM. Decreased glucose utilization was the predominant finding and was observed in 20% of the regions evaluated, with median raphe, vestibular nucleus, cerebellar vermis, and various structures associated with the auditory system showing the greatest reductions. The only structures that showed increased glucose utilization were the dentate region of the hippocampus and the superior olive, and this was only apparent at a blood ethanol concentration of 14 mM.

Animals↗
PubMed1988

The effect of pumiliotoxin-B on the excitability of bullfrog sympathetic neurons.

The effects of the alkaloid pumiliotoxin-B were investigated on neurons from bullfrog paravertebral ganglia using current-clamp techniques. Pumiliotoxin-B (2 microM) induced repetitive action potential discharge or bursting pacemaker activity in response to a single stimulus. The toxin had no significant effect on the mean resting potential or action potential characteristics of single action potentials evoked prior to the action potential discharge onset. During the action potential discharge, action potential threshold and afterhyperpolarization amplitude were decreased. In the presence of pumiliotoxin-B, single action potentials were followed by a depolarizing afterpotential. Pumiliotoxin-B still induced action potential discharge in Ca2+-free or Cd2+-containing solutions. Brief superfusion with a Na+-free or tetrodotoxin-containing solution abolished the pumiliotoxin-B-induced action potential discharge prior to the blockade of directly elicited single action potentials. These solutions decreased or abolished the depolarizing afterpotential. Pumiliotoxin-B increases membrane excitability and can induce a stimulation-dependent action potential discharge which appears to result from a tetrodotoxin-sensitive Na+-sensitive potential.

Action Potentials↗
PubMed1988

Single K+ channels activated by D2 dopamine receptors in acutely dissociated neurons from rat corpus striatum.

Corpus striatum neurons acutely dissociated from the brains of young adult rats had membrane surfaces suitable for G omega-seal recording. Whole-cell current-clamp and voltage-clamp recordings indicated that the cells remained electrically excitable after dissociation. Cell-attached recordings frequently revealed single-channel openings in the presence of dopamine or of the D2 dopamine agonist quinpirole. Channel openings were rarely or never observed in the absence of drugs or in the presence of quinpirole plus the dopamine antagonist haloperidol. The D2 antagonist spiperone was more potent at blocking the appearance of the channel than was the D1 antagonist SCH-23390. The channel reversal potential varied with the extracellular K+ concentration as predicted by the Nernst equation. The channel current-voltage relationship was linear, with a conductance of approximately equal to 85 pS in the presence of 140 mM KCl. These results are consistent with the opening of single K+ channels following D2 dopamine receptor activation.

Action Potentials↗
PubMed1988

Effects of long-term ethanol inhalation on the immune and hematopoietic systems of the rat.

An inhalation method of ethanol administration was used to study the effects of 14 days of ethanol administration on the immune and hematopoietic systems of the rat. A decrease in cellularity was found in the spleen, thymus, and bone marrow of ethanol-treated rats. Although the red blood cell count, white blood cell count, and hemoglobin concentration were not significantly different between treatment and control groups, treatment with ethanol altered the relative proportion of lymphocytes and polymorphonuclear leukocytes in the peripheral blood. The granulocyte-macrophage progenitor cells in the bone marrow were unaffected by ethanol treatment, but a significant decline in the number of erythroid progenitor cells was noted in ethanol-treated rats. Splenic lymphocytes, although fewer in number in the ethanol-treated rats, showed no significant difference in ability to proliferate when stimulated by nonspecific mitogens.

Administration, Inhalation↗
PubMed1988

Characterization of membrane currents in dissociated adult rat pineal cells.

1. Membrane currents, particularly the outward components, were studied in pineal cells acutely dissociated from adult rats using the whole-cell variant of the patch-clamp technique. 2. In current clamp, outward constant current elicited a transient graded depolarizing response. A sustained membrane rectification developed within 20 ms; this phenomenon was reduced in cells internally dialysed with 120 mM-CsCl. 3. Study of the membrane current revealed the existence of a transient and a delayed outward current. These currents were virtually eliminated when the cell was internally dialysed with CsCl. 4. The delayed outward current, isolated from a holding potential of -50 mV, activated at potentials near -20 mV, reached a steady-state current amplitude within 60 ms and had little or no decay during steps up to 400 ms in duration. This component was reduced by 80% or more with the addition of 5 mM-TEA. 5. From -100 mV, the transient outward current reached a peak within 15 ms and decayed with a single-exponential time course. The mean decay time constant was 66 +/- 10 ms (at -33 mV) and it showed little voltage sensitivity. This current, which activated at potentials positive to -60 mV and displayed half-inactivation at -76 +/- 8 mV, was reduced by 50% with the addition of 5 mM-4-AP (4-amino-pyridine). 6. In the presence of external Ca2+, the current-voltage relationship for the delayed current did not display a region of negative-slope conductance (N-shape). Increasing the intracellular ionized Ca2+ concentration by varying the Ca-EGTA buffer ratio did not alter the dependence of the current on the membrane potential. 7. Block of outward currents with internal Cs+ revealed a small (less than 90 pA) inward Ca2+ current when the external Ca2+ concentration was increased to 10 mM. From a holding potential of -50 mV, it had a threshold at -30 mV and peaked at +5 mV. Evidence for an inward Na+ current was not obtained. 8. We conclude that acutely dissociated pineal cells display two distinct K+ currents: (i) a slowly activating, sustained current similar to the delayed rectifier (IK); and (ii) a transient A-current (IA). At normal Ca2+ concentrations, no macroscopic Ca2+-activated outward current was observed.

4-Aminopyridine↗
PubMed1988

The protein kinase C activator 1-oleoyl-2-acetylglycerol inhibits voltage-dependent Ca2+ current in the pituitary cell line AtT-20.

The role of protein kinase C in regulating Ca2+ channel activity was investigated using the whole-cell patch-clamp technique in the mouse pituitary tumor cell line AtT-20. The Ca2+ current was activated by depolarizing voltage steps from a holding potential of -80 mV. Extracellular application of the protein kinase C activator 1-oleoyl-2-acetylglycerol (OAG) reduced voltage-dependent Ca2+ current. This effect was reversible and dose dependent (10-100 microM). Pertussis toxin did not block the effect of OAG on Ca2+ current, suggesting that OAG does not affect Ca2+ channels via a pertussis toxin sensitive guanosine triphosphate binding protein. Na+-free solutions did not block the effect of OAG on Ca2+ channels, suggesting that this effect of OAG does not involve the Na+/H+ antiporter. The phorbol esters 12-deoxyphorbol-13-isobutyrate (10 microM) and phorbol-12,13-diacetate (100 microM) also reduced Ca2+ current. The results suggest that protein kinase C may be an inhibitory regulator of voltage-dependent Ca2+ channels.

Animals↗
PubMed1988

Voltage-clamp models for the study of acute and chronic effects of ethanol on ionic currents in adult mammalian neurons.

The aim of this study was to develop and characterize a model system in which the effects of ethanol on voltage- and agonist-gated ionic currents in adult mammalian neurons could be studied using voltage-clamp techniques. We have found that neurons enzymatically isolated from the peripheral (nodose and superior cervical ganglia) and central nervous system (pyramidal layer of the hippocampus) of the adult rat and guinea pig provide several advantages over conventional neuronal preparations (e.g., intact ganglia or brain slice). First, the isolated neurons, in conjunction with the patch clamp technique, allow high fidelity recordings of both macroscopic and single channel currents. Secondly, current- and voltage-clamp recordings have revealed that active and passive membrane properties, chemosensitivity, and ionic currents in the isolated neurons resemble those described from conventional preparations. Finally, we have developed an intracellular perfusion system which allows the convenient control of the intracellular milieu. This technique should be useful for the study of intracellular second messengers on ionic currents. Our results demonstrate that isolated adult mammalian neurons are ideally suited for the study of both the acute and chronic effects of ethanol on membrane excitability.

Animals↗
PubMed1988

Ethanol's effects on neurotransmitter release and intracellular free calcium in PC12 cells.

The effect of ethanol on muscarine-stimulated release of [3H]NE was studied using the rat pheochromocytoma cell line, PC12. At concentrations of 25 mM and above, ethanol produced a dose dependent inhibition of muscarine-stimulated release of [3H]NE. The inhibition of muscarine-stimulated transmitter release occurred in the absence of any effect of ethanol on [3H]NE uptake, metabolism or on muscarinic binding to the cells. However, ethanol produced an inhibition of muscarine-stimulated elevation of intracellular free Ca2+ which corresponded with the inhibition of transmitter release. At concentrations greater than 100 mM, ethanol produced both a stimulation of the release of [3H]NE as well as an increase in intracellular free Ca2+. The increase in basal transmitter release and intracellular free Ca2+ occurred independent of the inhibition by ethanol of muscarine-stimulated elevation of intracellular free Ca2+ or transmitter section. These results demonstrate the relationship of the effects of ethanol on cellular free Ca2+ and neurotransmitter release.

Animals↗
PubMed1988

Effects of ethanol on neurotransmitter release and intracellular free calcium in PC12 cells.

The effect of ethanol on muscarine-stimulated release of l-[3H]norepinephrine ([3H]NE) was studied using the rat pheochromocytoma cell line, PC12. At concentrations of 25 mM and above, ethanol produced a dose-dependent inhibition of muscarine-stimulated release of [3H]NE. The inhibition of muscarine-stimulated transmitter release occurred in the absence of any detectable effect of ethanol on [3H]NE uptake or on muscarinic binding to the cells. However, ethanol produced an inhibition of muscarine-stimulated elevation of intracellular free Ca++ which corresponded with the inhibition of transmitter release. At concentrations greater than 100 mM, ethanol produced an increase in the basal release of [3H]NE. Intracellular free Ca++ also was increased by ethanol concentrations greater than 100 mM. The elevation of basal transmitter release and intracellular free Ca++ by concentrations of ethanol greater than 100 mM occurred independently of the inhibition by ethanol of muscarine-stimulated elevation of intracellular free Ca++ and transmitter secretion. These results suggest that the effects of ethanol on neurotransmitter release are associated with the effects of ethanol on intracellular free Ca++.

Adrenal Gland Neoplasms↗
PubMed1987

MPDP+ causes a non-reversible decrease in neostriatal synaptic transmission in mouse brain slice.

MPTP causes a Parkinson's disease-like syndrome in man and certain other animals. The toxic effect occurs if monoamine oxidase B is available, indicating that an MPTP metabolite may cause the toxic effect. We tested the effect of MPDP+, the first product of MPTP oxidation, and found that it, like MPTP, caused a non-reversible decrease in synaptic transmission in the mouse brain slice preparation. As the second oxidation product, MPP+ had been shown not to cause a similar, non-reversible decrease in synaptic transmission, MPDP+ is a better candidate for the role of toxic substance.

Animals↗
PubMed1987

Somatostatin blocks a calcium current in acutely isolated adult rat superior cervical ganglion neurons.

Somatostatin-like immunoreactivity has been reported to occur in the postganglionic neurons of sympathetic ganglia. We therefore investigated the effect of somatostatin (SOM) on the Ca2+ current in sympathetic neurons. Voltage-clamp recordings, using the whole-cell patch-clamp technique, were made from acutely isolated adult rat superior cervical ganglion (SCG) neurons in solutions (external and internal) designed to isolate Ca2+ currents. Application of 0.001-1.0 microM [D-Trp8]SOM resulted in a rapid, reversible and concentration-dependent decrease in the amplitude of the Ca2+ current evoked from a holding potential of -80 mV. The concentration-response relationship for SOM could be fitted to a single-site binding model with an apparent dissociation constant of 11 nM; the maximal attainable block of Ca2+ current by SOM was 50%. SOM also produced a pronounced slowing of the Ca2+ current rising phase, especially at more depolarized potentials. At higher concentrations (0.03-1.0 microM), prolonged application of SOM resulted in a progressive decrease in blocking ability. The results are consistent with a neurotransmitter and/or neuromodulator role for SOM in the sympathetic nervous system.

Animals↗
PubMed1987

Antagonists discriminate muscarinic excitation and inhibition in sympathetic ganglion.

The effect of muscarinic antagonists was studied on the muscarinic slow IPSP (inhibitory postsynaptic potential) and slow EPSP (excitatory postsynaptic potential) in bullfrog sympathetic ganglia using the sucrose-gap recording method. Pirenzepine, alcuronium and atropine reduced slow IPSP amplitude more than slow EPSP amplitude. The most selective antagonists studied were pancuronium and gallamine which blocked or substantially reduced the slow IPSP without significantly affecting slow EPSP amplitude. The results suggest that the muscarinic inhibitory response may involve a different muscarinic receptor subtype, and/or receptor-ion-channel complex, than the muscarinic excitatory response.

Alcuronium↗