Hyperpolarization‐activated currents in presynaptic terminals of mouse cerebellar basket cells

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Abstract
Using patch-clamp techniques, a hyperpolarization-activated current (Ih) was recorded from synaptic terminals of mouse cerebellar basket cells. Ih was blocked quickly and reversibly by 2 mM Cs+, and subtraction revealed a rapidly activating and deactivating Ih current. Similar gating and block of presynaptic Ih were also seen with the more selective inhibitor ZD 7288 (10 μM). The time constant of activation (τa) of presynaptic Ih current became faster with membrane hyperpolarization, being ≈74 ms at -130 mV, changing e-fold for a 33 mV change in membrane potential. Whole-cell recordings from basket cell somata also revealed an Ih current, which was similarly sensitive to block by ZD 7288. Inhibition of Ih by 10 μM ZD 7288 reduced the frequency (≈34 %) and amplitude (≈26 %) of spontaneous IPSCs (sIPSCs) recorded in Purkinje cells, one of the principal synaptic targets of basket neurones. This is the first report of an Ih current in mammalian inhibitory presynaptic terminals, which may be an important target for neuromodulation in the cerebellum. Comparing the biophysical properties and distribution of cloned hyperpolarization-activated cation channels, we also suggest a molecular candidate underlying Ih at these synapses.