A hyperpolarization activated inward current in histamine neurons

Several lines of evidence suggest that the histamine neurons of tuberomammillary (TM) nucleus are involved in control of behavioural state. H, receptor antagonists which cross the blood-brain barrier cause sedation, presumably the action >f neuronal histamine on HI receptors in the brain. TM neurons, which are spontaneously in aioo and in uirro, exhibit stereotypical changes in fii rate across behavioural states r. This state related firing pattern probably arises via li8andgated modulation of the ionic currents responsible for the sporitaneous activity of TM neurons. One current which might be a target for such modulation is the hyperpolarixation activated inward current Zb_We have used the single electrode voltage clamp technique to study the properties of 1, in TM neurons maintained in slices irr vitro a=. The steady-state current-voltage relationship of TM neurons exhibits inward rectification below -75 mV. Under convol conditions using standard superfusing solutions coAt~g 2.5 mM K+ and 126 mM Na+ h~e~l~g vobage steps from a holding potential of -50 mV evoked a slowly-developing non-inactivating inward current. This current wm reversibly reduced by extraceBular Cs+ (1 m?q and Ba2+ (2 mM), while removal of Ca2+ from the medium had no effect on the inward current. Raising extraceklar K+ from 2.5 to 10 mM increased the current at all potentials. Equimolar replacement of extraceklar Na+ by chohne reduced the inward current, and caused an ~st~t~~~ outward current at a holding potential of -50 mV, suggesting that this current is tonically active near

the x-es*&potentid. These data suggest that TM ne-uons possess a hyperpolarization

activated inward current, carried by K” and Na+ ions, which seems to be similar to I,, previously described in other cell types, This voltage-dependent inward current appears to be a candidate pacemaker current in these Ceus, contributing to the subthreshold inward current, and may play an important role in repetitive action potential generation in histamine neurons. ~up~~~

by the MRC of Canada. PBR is an MRC !Scholar

1. Vami-Mercier, G.. Sakai, K. and Jouvet, M., 1984, CR Acad Se. Paris 298,195, 2. Maas, N.L. and Reiner, P.B., 1988.) Physiol. (Land.) 399,633. 3. Greene, R.uI., Haas, N.L. a& Reiner, P-B., 1990,J. Physiol. (Land.) 420,149.

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*, P.B. and Haas **, H.L.

* KJnrmenLoborizti?tyof Neurological Research, Dept. of Psychiatry, Univ. of British Columbia, Vancouver, BC, Canada and

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* Dept. of Physiofow, Johannes Gutenberg Univetsity, Mainz, F.R. G.

The responses of histaminergic neurons d the tuberom~la~ (TM) nucleus of the hypothalamus to exogeno&y applied GABA were studied using intracellular recordings and single-electrode voltage clamp (SEVC) in an in vitro slice preparation (Haas and Reiner, 1988; Greene et al., 1990). GABA was applied either by bath application or by pressure ejecticn from an independent coarse-tipped pipette. en electrodes containing either K-acetate or K-methylsulfate were used, GABA app~ca~io~ produced a