HCN hyperpolarization-activated cation channels inhibit EPSPs by interactions with M-type [K.sup.+] channels

The processing of synaptic potentials by neuronal dendrites depends on both their passive cable properties and active voltage-gated channels, which can generate complex effects as a result of their nonlinear properties. We characterized the actions of HCN (hyperpolarization-activated cyclic nucleotide-gated cation) channels on dendritic processing of subthreshold excitatory postsynaptic potentials (EPSPs) in mouse CA1 hippocampal neurons. The HCN channels generated an excitatory inward current ([I.sub.h]) that exerted a direct depolarizing effect on the peak voltage of weak EPSPs, but produced a paradoxical hyperpolarizing effect on the peak voltage of stronger, but still subthreshold, EPSPs. Using a combined modeling and experimental approach, we found that the inhibitory action of [I.sub.h] was caused by its interaction with the delayed-rectifier M-type [K.sup.+] current. In this manner, [I.sub.h] can enhance spike firing in response to an EPSP when spike threshold is low and can inhibit firing when spike threshold is high.