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

1. Using patch-clamp techniques, a hyperpolarization-activated current (I-h ) was recorded from synaptic terminals of mouse cerebellar basket cells. 2. I-h was blocked quickly and reversibly by 2 mM Cs+, and subtraction reve aled a rapidly activating and deactivating I-h current. Similar gating and block of presynaptic I-h were also seen with the more selective inhibitor Z D 7288(10 mu M). 3. The time constant of activation (tau(a)) of presynaptic I-h current beca me faster with membrane hgperpolarization, being similar to 74 ms at -130 m V, changing e-fold for a 33 mV change in membrane potential. 4. Whole-cell recordings from basket cell somata also revealed an I-h curre nt, which was similarly sensitive to block by ZD 7288. 5. Inhibition of I-h by 10 mu M ZD 7288 reduced the frequency (similar to 3 4 %) and amplitude (similar to 26 %) of spontaneous IPSCs (sIPSCs) recorded in Purkinje cells, one of the principal synaptic targets of basket neurone s. 6. This is the first report of an I-h current in mammalian inhibitory presy naptic terminals, which may be an important target for neuromodulation in t he cerebellum. Comparing the biophysical properties and distribution of clo ned hyperpolarization-activated cation channels, we also suggest a molecula r candidate underlying I-h at these synapses.