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H L Haas

Publications and source records attributed to H L Haas.

149 records · Page 9Linked to original sources
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Long-term increase of hippocampal excitability by histamine and cyclic AMP.

The action of histamine (HA) on rat hippocampal CA1 pyramidal cells in vitro was investigated in slices perfused with solution containing 0.2 mM Ca2+/4.0 mM Mg2+. Extracellular recordings of the spontaneous discharges occurring under these conditions revealed that HA caused a long-lasting increase in cell firing. The HA-effects were dose-dependent, in that low concentrations of HA (0.1-0.5 microM) exhibited an initial transient depression of cell firing and practically no long-lasting action, whereas higher concentrations of HA (1-10 microM) exerted strong, non-declining increases. The H1-receptor antagonist mepyramine (1 microM) blocked the initial depression of firing and attenuated the long-lasting HA-mediated excitation. Pure H1-receptor activation, tested with the H1-receptor agonist 2-(3-fluorphenyl)histamine (1-10 microM) depressed cell firing, similar to the low dose effects of HA. HA-induced excitations were prevented by the H2-receptor antagonist cimetidine (10-50 microM), and mimicked by the very potent H2-receptor agonist impromidine (1 or 3 microM) which was, however, less effective compared to equal concentrations of HA. H3-receptor activation by R-alpha-methylhistamine had no significant effect on cell firing. Thus, histamine H1 and H2 receptors seem to cooperate in producing this long-lasting augmentation of excitability. 8-Bromo-cyclic AMP monophosphate (8-Br-cAMP, 50-100 microM) mimicked the long-term excitation, whereas the adenylyl-cyclase inhibitor 9-tetrahydro-2-furyladenine (THFA, 100-500 microM) or the PKA-inhibitor Rp-adenosine-3'5'-cyclic monophosphate (Rp-cAMPS, 10 microM) blocked it, indicating that the HA-mediated increase of excitability in the hippocampus is dependent on the adenylate cyclase/PKA-signal transduction cascade. DL-2-Amino-5-phosphonopentanoic acid (APV, 50 microM) significantly attenuated the magnitude of the HA-induced enhancement, indicating an NMDA receptor-dependent component. Other biogenic amines, acting through receptors positively coupled to adenylyl cyclase, elicited similar responses as HA, indicating common mechanisms by which these substances modulate excitability in CA1 pyramidal cells.

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Histamine and noradrenaline decrease calcium-activated potassium conductance in hippocampal pyramidal cells.

Ample evidence exists for histaminergic and noradrenergic projections to the hippocampus. Both amines exert neurotransmitter or modulator actions on principal neurones in the CA 1 and in the dentate area. A number of mechanisms have been proposed for these actions, including increased potassium conductance, increased chloride conductance and electrogenic pump stimulation, and reduction of the anomalous inward rectification. Action potentials, and particularly bursts of spikes, in CA 1 pyramidal cells, are followed by an afterhyperpolarization (AHP) which consists of two components. The late AHP depends on a calcium-activated potassium conductance gK+ (Ca2+), and has recently been shown to be increased by dopamine. We report here a rapid and reversible decrease of the late AHP component following a burst of sodium spikes or a calcium spike, during perfusion with micromolar concentrations of histamine and noradrenaline. This effect is mediated by H2 receptors and beta-receptors, respectively, and occurred in the absence of changes in the calcium spike. By such a mechanism histamine and noradrenaline can profoundly potentiate the excitatory impact of depolarizing signals.

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[Hippocampal ripple oscillations (200 Hz) in mechanisms of memory consolidation].

A current status of knowledge about high-frequency (140-200 Hz) ripple oscillations in the CA1 hippocampal subfield is summarized and considered in the context of two-stage model of the hippocampal memory processing. A large body of evidence suggests highly-selective recruitment of pyramidal cells and interneurons in the generation of the oscillatory pattern after co-operative sharp-wave-related discharge of CA3 pyramidal neurons. We also discuss a role of transmission via gap junctions in the mechanisms of ripple oscillations as well as their adaptive aminergic (histaminergic) modulation. Patterns of neuronal firing in the hippocampus observed during ripple oscillations reproduce space-dependant neuronal activity from the previous waking period. Together with a data about efficacy of high-frequency stimulation for induction of synaptic modification it points out a role for ripples in the formation of long-term memory. Focal ultra fast ripples (up to 500 Hz) have been shown to participate in the development of temporal lobe epilepsy.

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Blockade of mammalian and invertebrate calcium channels by lead.

We have compared the effects of Pb2+ on voltage-dependent calcium channels of the marine mollusc Aplysia, studied with a two electrode voltage clamp, with those on calcium channels in cultured rat dorsal root ganglion (DRG) neurons studied with whole cell patch clamp. In both preparations Pb2+ was a potent blocker of calcium channel currents at concentrations that did not significantly affect potassium and sodium currents. The blockade was concentration dependent and the percentage of blockade was reduced when the concentration of the charge carrier was elevated. In Aplysia the threshold Pb2+ concentration was about 1 microM, and the Hill coefficient near 1.0 under all conditions. Pb2+ did not significantly change inactivation but shifted the voltage dependence of activation to hyperpolarized voltages in a dose-dependent manner. The blockade of calcium currents by Pb2+ was highly voltage dependent and increased with depolarization. Rat dorsal root ganglion cells exhibit three different types of voltage-dependent calcium channels (N, L and T) which can be distinguished by the potential at which the channel activates or inactivates and by their sensitivity to pharmacologic antagonists. The IC50 for blockade of the L current was 1.03 microM with a Hill slope of 1.15. Currents elicited by voltage steps which activate N plus L currents had an IC50 of 0.64 microM and a Hill slope of 1.16. T currents were less sensitive, having an IC50 of 6 microM. Sodium and potassium currents were relatively unaffected in both preparations at concentrations at which the calcium channel was blocked more than 60% (1 microM or 200 microM respectively). The blockade in DRG neurons was less voltage-dependent and reversible than that in the invertebrate model system. These observations indicate that Pb2+ is a potent, reversible and selective blocker of voltage-dependent calcium channels at low concentrations.

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