Modulation of neuronal firing mode in cat and guinea pig LGNd by histamine: possible cellular mechanisms of histaminergic control of arousal

Abstract

The thalamus is innervated by histaminergic fibers presumably arising from neurons in the tuberomammillary nucleus of the hypothalamus. The possible function of this histaminergic projection was addressed through investigation of the cellular actions of histamine on guinea pig and cat dorsal lateral geniculate (LGNd) relay neurons maintained as a slice in vitro. Local application of histamine to LGNd relay neurons resulted in a slow depolarization that was associated with a decrease in membrane conductance and was blocked by the H1-antagonists pyrilamine, triprolidine, or diphenhydramine. Current versus voltage relationships revealed that the slow depolarization was associated with an inward current that reversed near EK, indicating that it was due to a decrease in a potassium current. The slow depolarizing response to histamine was occluded by maximal activation of the slow depolarizing responses resulting from stimulation of alpha 1-adrenergic or muscarinic receptors, suggesting that they are all mediated by reduction in the same potassium current and/or alteration of a common second messenger. In the presence of H1-receptor antagonists, application of histamine resulted in a small depolarization that was associated with a marked increase in apparent membrane conductance. Voltage-clamp recordings revealed that this response was associated with enhancement of the hyperpolarization-activated cation current Ih. This response to histamine was blocked by local or bath application of the H2-antagonists cimetidine or tiotidine. The functional consequences of these actions of histamine were addressed with extracellular and intracellular recordings in guinea pig and cat LGNd relay neurons. Extracellular recordings in cat LGNd revealed the occurrence of highly regular 1-4 Hz rhythmic burst discharges. Application of histamine halted rhythmic bursting and replaced it with a prolonged period of single-spike activity. Intracellular recordings indicate that the histamine-induced switch in firing mode is due largely to the slow depolarizing response mediated by H1-receptors, but is also facilitated by the enhancement of Ih mediated by H2-receptors. These postsynaptic actions indicate that increased activity in the tuberomammillary histaminergic system may result in a switch of thalamic neuronal activity from rhythmic burst firing to single-spike activity and thereby promote the accurate transmission and processing of sensory information and cognition.

Protein kinase C-dependent inhibition of K+ currents in noradrenaline-induced depolarization of smooth muscle of guinea-pig vas deferens

“…Together, these findings indicate that activation of PKC is involved in the NAinduced reduction in the K¤ currents of the smooth muscle of the guinea-pig vas deferens. Involvement of a PKC-dependent phosphorylation in the decrease in K¤ conductance has been reported in a variety of cell types, including neurons (Madison et al 1987;Benson et al 1988;McCormick & Williamson, 1991;Munakata & Akaike, 1994;Li & Hatton, 1996), atrial myocytes (Sato & Koumi, 1995) and epithelial cells (Tabcharani et al 1994). In smooth muscle cells, on the other hand, only a little is known of the PKC action on the K¤ current, and the action so far reported varies in different tissues.…”

The role of potassium channels in antihistamine analgesia

“…The Ca 2 + -activated K + current in rat hippocampal neurones was suppressed by histamine (Haas and Konnerth, 1983). Histamine decreased a resting or 'leak' K + current and shifted the voltage dependency of a hyperpolarizationactivated current in the lateral geniculate nucleus of the guinea-pig (Mc Cormick and Williamson, 1991) as well as reduced K + currents in neostriatal interneurones (Munakata and Akaike, 1994). Furthermore, the involvement of the H 1 receptor subtype in the block of K + currents produced by histamine has been reported (Munakata and Akaike, 1994;Jafri et al, 1997).…”

Theoretical aspects of sensory substitution and of neurotransmission-related reorganization in spinal cord injury

“…5,42 Many functions may be produced by combinations of both types of neurotransmission. In the piano playing example presented above, in addition to the relevant synaptic mechanisms, the ®nger movements can be more precise in the presence of adequate preparation including changes in brain tone (probably mediated by noradrenaline), and the visual perception of the tennis game may require neuronal receptivity to be set at a high level, probably involving several neurotransmitters, including nitric oxide 50 and dopamine 51 in the retina, serotonin and histamine in the lateral geniculate nucleus 52,53 and noradrenaline in the visual cortex. 54 These e ects appear to be primarily non-synaptically mediated.…”