Hyperpolarization-activated currents in presynaptic terminals of mouse cerebellar basket cells.
Using patch-clamp techniques, a hyperpolarization-activated current (I(h)) 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 I(h) current. Similar gating and block of presynaptic I(h) were also seen with the more selective inhibitor ZD 7288 (10 microM). The time constant of activation (tau (a))of presynaptic I(h) current became faster with membrane hyperpolarization, being approximately 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 I(h) current, which was similarly sensitive to block by ZD 7288. Inhibition of I(h) by 10 microM ZD 7288 reduced the frequency ( approximately 34 %) and amplitude ( approximately 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 I(h) 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 I(h) at these synapses.
Southan
A P
AP
Neuronal Excitability Group, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2BZ, UK.
Morris
N P
NP
Stephens
G J
GJ
Robertson
B
B
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002586:Cesium / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D004305:Dose-Response Relationship, Drug; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009419:Nerve Tissue Proteins; D009433:Neural Inhibition / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002317:Cardiovascular Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D011743:Pyrimidines; D018091:Receptors, AMPA; C082246:ICI D2788; D002586:Cesium; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione