I h from synapses to networks: HCN channel functions and modulation in neurons

Hyperpolarization-activated cyclic nucleotide gated (HCN) channels and the current they carry, I h, are widely and diversely distributed in the central nervous system (CNS). The distribution of the four subunits of HCN channels is variable within the CNS, within brain regions, and often within subcellular compartments. The precise function of I h can depend heavily on what other channels are co-expressed. In this review, we give an overview of HCN channel structure, distribution, and modulation by cyclic adenosine monophosphate (cAMP). We then discuss HCN channel and I h functions, where we have parsed the roles into two main effects: a steady effect on maintaining the resting membrane potential at relatively depolarized values, and slow channel dynamics. Within this framework, we discuss I h involvement in resonance, synaptic integration, transmitter release, plasticity, and point out a special case, where the effects of I h on the membrane potential and its slow channel dynamics have dual roles in thalamic neurons.