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Objective The globus pallidus (GP) plays a significant role in motor control under both health and pathological states.Recent studies have revealed that hyperpolarization activated cyclic-nucleotide gated (HCN) channels occupies a critical position in GP pacemaking activity.Morphological studies have shown the expression of HCN channel in GP.Previous in vitro patch cIamp recordings revealed that HCN channels are involved in the regulation of the spontaneous firing of GP.The present study is to investigate the in vivo effects of HCN channels in the GP under normal and parkinsionian states.Methods In vivo extracellular recordings were performed in the present study.Results (1) In normal rats, micropressure ejection of 0.5 mM ZD7288, the relatively selective HCN channel antagonist, decreased the frequency of spontaneous firing from 13.9±2.6 Hz to 6.4±1.6 Hz (n=11, P<0.01) in 11 out of the 30 pallidal neurons.In 18 out of the 30 pallidal neurons with the basal firing rate of 8.7±1.0 Hz, ZD7288 increased the firing rate to 16.5±1.8 Hz.(2) In 6-hydroxydopamine (6-OHDA) parkinsonian rats, on the lesioned side, local administration of ZD7288 decreased the firing rate from 6.1±1.6 Hz to 3.2±1.4 Hz (n=9, P<0.01) in 9 out of 20 pallidal neurons.In another 9 pallidal neurons, ZD7288 increased the firing rate from 6.8±1.8 Hz to 15.8±3.5 Hz (n=9, P<0.01).On the unlesioned side, ZD7288 administration decreased the firing rate from 12.2±2.2 Hz to 5.8±1.6 Hz in 8 out of the 16 neurons recorded.In 6 out of the 16 neurons, ZD7288 increased the firing rate from 7.4±2.3 Hz to 12.5±2.5 Hz.The ZD7288-induced increase in firing rate on the lesioned side of 6-OHDA parkinsonian rats was stronger than that in normal rats (P<0.05).Conclusion The present electrophysiological findings sugguests that pharmacological block of HCN channels on pallidal neurons in normal and parkinsonian rats has different electrophysiological effects in vivo.It may provide a rationale for further investigations into the roles of HCN channels in the GP under normal and Parkinsonism state.