Histamine depolarizes cholinergic interneurones in the rat striatum via a H-1-receptor mediated action

1 Whole-cell patch clamp recordings were made from rat striatal cholinergic interneurones in slices of blain tissue in vitro. Bath application of hist amine (EC50 6.3 muM) was found to rapidly and reversibly depolarize those n eurones through the induction of an inward current at -60 mV. 2 The effects of histamine were mimicked by the H-1 receptor agonist 2-thia zolylethylamine (50 muM) and selectively inhibited by pre-incubation with t he H-1 receptor antagonist triprolidine (1 muM). 3 Ion substitution experiments under voltage clamp conditions revealed that the histamine activated current was comprised of two components. One compo nent was sensitive to the concentration of extracellular Na+, whilst the ot her component was inhibited by intracellular Cs+ or extracellular Ba24 In situ hybridization experiments revealed that the majority of cholinerg ic interneurones in the rat striatum express the histamine H-1 receptor but few neurones express H-2 receptors. These findings were confirmed using si ngle cell RT-PCR. 5 It is concluded that histamine depolarizes cholinergic interneurones in t he rat striatum via a H-1-receptor mediated mechanism.