Hyperpolarization-activated cation channels in fast-spiking interneurons of rat hippocampus

Hyperpolarization-activated channels (I-h or HCN channels) are widely expressed in principal neurons in the central nervous system. However, I-h in inhibitory GABAergic interneurons is less well characterized. We examined the functional properties of I-h in fast-spiking basket cells (BCs) of the dentate gyrus, using hippocampal slices from 17- to 21-day-old rats. Bath application of the I-h channel blocker ZD 7288 at a concentration of 30 mu m induced a hyperpolarization of 5.7 +/- 1.5 mV, an increase in input resistance and a correlated increase in apparent membrane time constant. ZD 7288 blocked a hyperpolarization-activated current in a concentration-dependent manner (IC50, 1.4 mu m). The effects of ZD 7288 were mimicked by external Cs+. The reversal potential of I-h was -27.4 mV, corresponding to a Na+ to K+ permeability ratio (P-Na/P-K) of 0.36. The midpoint potential of the activation curve of I-h was -83.9 mV, and the activation time constant at -120 mV was 190 ms. Single-cell expression analysis using reverse transcription followed by quantitative polymerase chain reaction revealed that BCs coexpress HCN1 and HCN2 subunit mRNA, suggesting the formation of heteromeric HCN1/2 channels. ZD 7288 increased the current threshold for evoking antidromic action potentials by extracellular stimulation, consistent with the expression of I-h in BC axons. Finally, ZD 7288 decreased the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in hippocampal granule cells, the main target cells of BCs, to 70 +/- 4% of the control value. In contrast, the amplitude of mIPSCs was unchanged, consistent with the presence of I-h in inhibitory terminals. In conclusion, our results suggest that I-h channels are expressed in the somatodendritic region, axon and presynaptic elements of fast-spiking BCs in the hippocampus.