title: A special blocker reveals the presence and function of the hyperpolarization-activated cation current IH in peripheral mammalian nerve fibres.
abstract: Electrotonic responses recorded extra- or intracellularly from peripheral nerve preparations show a "sag" to hyperpolarizing current pulses. The biophysical nature of this "inward rectification" is still under discussion since the phenomenon has not been noted at voltage-clamped single nerve fibres, and since Cs+, which reduces inward rectification, is not a specific ion channel blocker. In this study, we found that low micromolar concentrations of ZD 7288, a specific blocker of the hyperpolarization-activated cationic current (Ih) in the soma of central mammalian neurons, result in a complete block of inward rectification in the electrotonic responses of isolated rat spinal dorsal roots. In addition, ZD 7288 enhanced the activity-dependent slowing of conduction seen in compound C fibre action potentials of isolated rat vagus nerves and augmented the post-tetanic hyperpolarization following trains of action potentials in unmyelinated and myelinated axons. The data suggest that ZD 7288 is a potent blocker and a useful research tool for the study of hyperpolarization-activated inward rectification (Ih) of peripheral nerve preparations.
authors.affiliation: Department of Physiology, University of Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Takigawa
authors.forename: C
authors.initials: C
authors.lastname: Alzheimer
authors.forename: S
authors.initials: S
authors.lastname: Quasthoff
authors.forename: P
authors.initials: P
authors.lastname: Grafe
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002586:Cesium / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D007473:Ion Channels; D011743:Pyrimidines; C082246:ICI D2788; D002586:Cesium