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  • 1
    Online-Ressource
    Online-Ressource
    Springer Science and Business Media LLC ; 1967
    In:  Nature Vol. 213, No. 5082 ( 1967-3), p. 1229-1230
    In: Nature, Springer Science and Business Media LLC, Vol. 213, No. 5082 ( 1967-3), p. 1229-1230
    Materialart: Online-Ressource
    ISSN: 0028-0836 , 1476-4687
    RVK:
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 1967
    ZDB Id: 120714-3
    ZDB Id: 1413423-8
    SSG: 11
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
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    American Physiological Society ; 1986
    In:  Journal of Neurophysiology Vol. 55, No. 3 ( 1986-03-01), p. 527-539
    In: Journal of Neurophysiology, American Physiological Society, Vol. 55, No. 3 ( 1986-03-01), p. 527-539
    Kurzfassung: The electrical properties of nodose ganglion cells acutely isolated from adult rats were studied using the whole-cell patch-clamp recording method. Current-clamp recordings revealed a mean resting membrane potential of -54.3 mV and an input resistance of 527 M omega. Depolarizing current steps evoked action potentials with the following properties (mean): amplitude 111 mV, threshold -36 mV, and rate of rise 117 V/s. Two types of action potentials were observed, short and long duration. These properties, with the exception of input resistance (527 M omega cf. 50 M omega), are similar to those reported previously using intracellular recording methods in intact nodose ganglia (11, 20, 28). Brief application of 10 microM 5-hydroxytryptamine resulted in a rapid depolarization and burst of action potentials in the majority of cells. With voltage-clamp recording, step depolarizations to potentials positive to -10 mV elicited a transient inward current that was followed by a sustained outward current. Inward Na+ current was isolated by ion substitution and pharmacological agents. Two types of Na+ current were observed. One current was completely abolished by 3-15 microM tetrodotoxin (TTX), had a rapid time course, activated over the potential range -60 to -10 mV, and attained half-maximal conductance at -30 mV. The other current persisted in the presence of 15 microM TTX, had a slower time course, activated over the potential range -30 to 0 mV, and attained half-maximal conductance at -15 mV. In addition, 500 microM Cd2+ and 5.0 mM Co2+ reduced the TTX-insensitive current to 53 and 42% of control, respectively. Inward Ca2+ current was isolated by ion substitution and pharmacological agents and was identified by a dependence on external Ca2+. Cd2+ (500 microM) and Co2+ (5 mM) reduced the maximal inward current to 5 and 20% of control, respectively. When Ba2+ was substituted for Ca2+ as the charge carrier, the maximal inward current increased to 175% of control. Some cells had two Ca2+ current components, an inactivating component that activated near -60 mV and a large sustained current that activated near -40 mV. The initial inactivating current appeared as a "hump" on the current-voltage (I-V) curve over the potential range of -60 to -30 mV. The results indicate that, following isolation of these adult mammalian neurons, the membrane surfaces are sufficiently clean to allow patch-clamp recording.(ABSTRACT TRUNCATED AT 400 WORDS)
    Materialart: Online-Ressource
    ISSN: 0022-3077 , 1522-1598
    RVK:
    Sprache: Englisch
    Verlag: American Physiological Society
    Publikationsdatum: 1986
    ZDB Id: 80161-6
    ZDB Id: 1467889-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Online-Ressource
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    American Physiological Society ; 1996
    In:  Journal of Neurophysiology Vol. 76, No. 5 ( 1996-11-01), p. 3048-3058
    In: Journal of Neurophysiology, American Physiological Society, Vol. 76, No. 5 ( 1996-11-01), p. 3048-3058
    Kurzfassung: 1. The modulation by protons of ATP-gated ion channel responses to ATP and Zn2+ was studied in freshly isolated rat nodose ganglion neurons using the whole cell patch-clamp technique. 2. Reduced external pH enhanced, whereas elevated external pH suppressed, current activated by 10 microM ATP. The pH producing the half-maximal effect (EC50) at this ATP concentration was 7.1. 3. Acidification shifted the ATP concentration-response curve to the left, decreasing the EC50 for ATP, and alkalinization shifted the ATP concentration-response curve to the right, increasing the EC50 for ATP. Fitting the data to a single-site pH model yielded an apparent pKa of the site on the ATP-gated ion channel of 7.6. Between pH 6.8 and 7.8, a change of 0.1 pH unit was calculated to change the ATP EC50 by 4.03 microM. Changing pH did not alter the maximal response to ATP. 4. The potentiating effect of protons appeared to be due to a direct action on the ATP-gated channel, as it could not be explained by an increase in the concentration of one or more species of ATP. 5. Lowering pH also increased the potency of Zn2+ for enhancement of ATP-activated current without altering its maximal response. Changing the pH from 7.3 to 6.8 changed the Zn2+ EC50 from 12 to 1.7 microM. 6. The potentiation of ATP-activated current by protons could not be attributed solely to an increase in the affinity of the receptor for Zn2+, as the Zn2+ chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine did not alter the effect of protons. 7. Protons and Zn2+ do not appear to act at the same site on ATP-gated channels, as responses to maximally effective concentrations of Zn2+ were enhanced further by protons and vice versa. 8. These results suggest that protons regulate the function of P2X purinoceptors in rat nodose ganglion neurons by modulating the affinity of the binding sites for ATP and Zn2+ on these receptor channels.
    Materialart: Online-Ressource
    ISSN: 0022-3077 , 1522-1598
    RVK:
    Sprache: Englisch
    Verlag: American Physiological Society
    Publikationsdatum: 1996
    ZDB Id: 80161-6
    ZDB Id: 1467889-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    Proceedings of the National Academy of Sciences ; 1986
    In:  Proceedings of the National Academy of Sciences Vol. 83, No. 23 ( 1986-12), p. 9035-9039
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 83, No. 23 ( 1986-12), p. 9035-9039
    Kurzfassung: Somatostatin reduces voltage-dependent Ca2+ current (ICa) and intracellular free Ca2+ concentration in the AtT-20/D16-16 pituitary cell line. We tested whether guanine nucleotide-binding proteins (G or N proteins) are involved in the signal transduction mechanism between the somatostatin receptor and voltage-dependent Ca2+ channels. Treatment of the cells with pertussis toxin, which selectively ADP ribosylates the GTP binding proteins Gi and Go and suppresses the ability of Gi to couple inhibitory receptors to adenylate cyclase, abolished the action of somatostatin on both ICa and intracellular free Ca2+. Intracellular application of the nonhydrolyzable guanine nucleotide analog guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S] ), which irreversibly activates G proteins, changed the somatostatin effect on ICa from a reversible to an irreversible inhibition. Intracellular GTP[gamma S] alone caused a very slowly developing inhibition of ICa. When ICa was inhibited by GTP[gamma S] (alone or with somatostatin), it failed to respond to subsequent applications of somatostatin. The effect of GTP[gamma S] on the inhibition of ICa by somatostatin was not altered by the intracellular application of cAMP and 3-isobutyl-1-methylxanthine. The results suggest that a GTP-binding protein is directly involved in the cAMP-independent receptor-mediated inhibition of voltage-dependent Ca2+ channels.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 1986
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    Proceedings of the National Academy of Sciences ; 1994
    In:  Proceedings of the National Academy of Sciences Vol. 91, No. 17 ( 1994-08-16), p. 8200-8204
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 91, No. 17 ( 1994-08-16), p. 8200-8204
    Kurzfassung: For almost a century, alcohols have been thought to produce their effects by actions on the membrane lipids of central nervous system neurons--the well known "lipid theory" of alcohol action. The rationale for this theory is the correlation of potency with oil/water or membrane/buffer partition coefficient. Although a number of recent studies have shown that alcohols can affect the function of certain neuronal neurotransmitter receptors, there is no evidence that the alcohols interact directly with these membrane proteins. In the present study, we report that inhibition of a neuronal neurotransmitter receptor, an ATP-gated ion channel, by a series of alcohols exhibits a distinct cutoff effect. For alcohols with a molecular volume of 〈 or = 42.2 ml/mol, potency for inhibiting ATP-activated current was correlated with lipid solubility (order of potency: 1-propanol = trifluoroethanol 〉 monochloroethanol 〉 ethanol 〉 methanol). However, despite increased lipid solubility, alcohols with a molecular volume of 〉 or = 46.1 ml/mol (1-butanol, 1-pentanol, trichloroethanol, and dichloroethanol) were without effect on the ATP-activated current. The results suggest that alcohols inhibit the function of this neurotransmitter receptor by interacting with a small hydrophobic pocket on the receptor protein.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 1994
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
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    Annual Reviews ; 1996
    In:  Annual Review of Pharmacology and Toxicology Vol. 36, No. 1 ( 1996-04), p. 185-201
    In: Annual Review of Pharmacology and Toxicology, Annual Reviews, Vol. 36, No. 1 ( 1996-04), p. 185-201
    Materialart: Online-Ressource
    ISSN: 0362-1642 , 1545-4304
    URL: Issue
    RVK:
    Sprache: Englisch
    Verlag: Annual Reviews
    Publikationsdatum: 1996
    ZDB Id: 1474461-2
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
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    American Physiological Society ; 1987
    In:  Journal of Neurophysiology Vol. 58, No. 6 ( 1987-12-01), p. 1431-1451
    In: Journal of Neurophysiology, American Physiological Society, Vol. 58, No. 6 ( 1987-12-01), p. 1431-1451
    Kurzfassung: 1. Voltage-clamp recordings were made from cultured AtT-20 pituitary cells using the whole-cell patch-clamp technique. Cells were perfused internally with Cs+ to block K+ currents and bathed externally with either 1 microM tetrodotoxin or with tetraethylammonium (TEA) as a Na+ substitute to block voltage-activated Na+ currents. 2. Depolarizing voltage steps from a holding potential of -80 mV to potentials positive to -30 mV evoked two currents: a fast inward current that activated between -30 and +70 mV and a slowly activating current (designated “slow step current”) that was inward between -30 and near 0 mV (the Cl- equilibrium potential) and outward positive to about 0 mV. Repolarization to -80 mV revealed a slowly decaying, inward tail current, whose magnitude with respect to step potential closely matched the current-voltage relationship of the voltage-activated Ca2+ current. 3. Activation of the fast inward current, slow step current, and tail current, was prevented by extracellular application of Cd2+ or removal of extracellular Ca2+. Replacement of extracellular Ca2+ with Ba2+ potentiated the fast inward current but blocked the slow step and tail currents. Intracellular perfusion with greater than 1 mM of the Ca2+ chelators ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) or [1,2-bis(2)aminophenoxy]ethane N,N,N',N'-tetraacetic acid (BAPTA) prevented activation of the slow step and tail currents, but not the fast inward current. 4. The reversal potential of the slow inward current was sensitive to changes in the Cl- equilibrium potential but not to substitution of TEA for Na+. The slow step current, but not the fast inward current, was partially blocked by the Cl- channel blocker, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid. 5. These data indicate that both the slow inward tail current and the slowly activating, reversible step current were a Ca2+-dependent Cl- current, similar to that described in other neuronal and nonneuronal cell types. The fast inward current was a voltage-activated Ca2+ current, described previously in these and other cells. 6. In the absence of intracellular EGTA, the tail current decayed with complex kinetics, its time course apparently dependent on the magnitude of the voltage-activated Ca2+ current. In the presence of 200 microM intracellular EGTA, the tail current decayed significantly faster and often decayed exponentially.
    Materialart: Online-Ressource
    ISSN: 0022-3077 , 1522-1598
    RVK:
    Sprache: Englisch
    Verlag: American Physiological Society
    Publikationsdatum: 1987
    ZDB Id: 80161-6
    ZDB Id: 1467889-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
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    Informa UK Limited ; 1988
    In:  Advances in Alcohol & Substance Abuse Vol. 7, No. 3-4 ( 1988-03), p. 95-97
    In: Advances in Alcohol & Substance Abuse, Informa UK Limited, Vol. 7, No. 3-4 ( 1988-03), p. 95-97
    Materialart: Online-Ressource
    ISSN: 0270-3106
    Sprache: Englisch
    Verlag: Informa UK Limited
    Publikationsdatum: 1988
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
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    Proceedings of the National Academy of Sciences ; 1995
    In:  Proceedings of the National Academy of Sciences Vol. 92, No. 7 ( 1995-03-28), p. 2825-2829
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 92, No. 7 ( 1995-03-28), p. 2825-2829
    Kurzfassung: As the number of carbon atoms in an aliphatic n-alcohol is increased from one to five, intoxicating potency, lipid solubility, and membrane lipid disordering potency all increase in a similar exponential manner. However, the potency of aliphatic n-alcohols for producing intoxication reaches a maximum at six to eight carbon atoms and then decreases. The molecular basis of this "cutoff" effect is not understood, as it is not correlated with either the lipid solubility or the membrane disordering potency of the alcohols, which continue to increase exponentially. Since it has been suggested that inhibition of N-methyl-D-aspartate (NMDA) receptors by alcohols may play a role in alcohol intoxication, we investigated whether a series of aliphatic n-alcohols would exhibit a cutoff in potency for inhibition of NMDA receptors. We found that although potency for inhibition of NMDA receptors increased exponentially for alcohols with one to five carbon atoms, potency for inhibition of NMDA receptors reached a maximum at six to eight carbon atoms and then abruptly disappeared. This cutoff for alcohol inhibition of NMDA receptors is consistent with an interaction of the alcohols with a hydrophobic pocket on the receptor protein. In addition, the similarity of the cutoffs for alcohol inhibition of NMDA receptors and alcohol intoxication suggests that the cutoff for NMDA receptor inhibition may contribute to the cutoff for alcohol intoxication, which is consistent with an important role of NMDA receptors in alcohol intoxication.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 1995
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
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    Proceedings of the National Academy of Sciences ; 1988
    In:  Proceedings of the National Academy of Sciences Vol. 85, No. 10 ( 1988-05), p. 3618-3622
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 85, No. 10 ( 1988-05), p. 3618-3622
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 1988
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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