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Hyperpolarization-activated,cyclic nucleotide-gated and cation-nonselective ion channels (Ih Channels,or HCN channels) play important roles in maintaining pacemaker activity of neurons and heart cells,regulation of membrane excitability,dendritic integration,and neuronal plasticity.Knock-out of individual Ih channel gene in mice leads to impaired learning and memory (HCN1),absence epilepsy and sinus dysrhythmia (HCN2),and heart contraction defect (HCN4).Ih channel genes are conserved in vertebrates and invertebrates.There is only a single gene encoding Ih channel in Drosophila melanogaster,providing an ideal model to study the physiological significance of Ih channels in vivo by knock-out technique.We carried out functional analysis of Drosophila Ih channel with mutants of transposon disruption of Ih channel gene.Drosophila Ih channel mutants are viable,fertile and developmentally normal,but with reduced lifespan.Reduced olfactory sensitivity and enhanced appetitive response in taste was observed in Drosophila Ih channel mutants.In contrast to their normal circadian rhythm and sleep,Drosophila Ih channel mutants are hyperactive and uncoordinated; and aged flies display seizure-like activity.We generated transgenic Gal4 flies of Ih promoter and examined the detailed expression pattern for Ih channel in larval and adult flies,which will provide clues to our understanding the molecular and cellular mechanisms underlying the role of Ih channel in Drosophila.