A SPECIFIC BLOCKER REVEALS THE PRESENCE AND FUNCTION OF THE HYPERPOLARIZATION-ACTIVATED CATION CURRENT I-H IN PERIPHERAL MAMMALIAN NERVE-FIBERS

Electrotonic responses recorded extra-or intracellularly from peripher al nerve preparations show a ''sag'' to hyperpolarizing current pulses .(10,11,20) The biophysical nature of this ''inward rectification'' is still under discussion since the phenomenon has not been noted at vol tage-clamped single nerve fibres, and since Cs+, which reduces inward rectification, is not a specific ion channel blocker, In this study, w e found that low micromolar concentrations of ZD 7288, a specific bloc ker of the hyperpolarization-activated cationic current (I-h) in the s oma of central mammalian neurons,(8) result in a complete block of inw ard rectification in the electrotonic responses of isolated rat spinal dorsal roots, In addition, ZD 7288 enhanced the activity-dependent sl owing of conduction seen in compound C fibre action potentials of isol ated 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 rect ification (I-h) of peripheral nerve preparations. (C) 1997 IBRO. Publi shed by Elsevier Science Ltd.