A specific blocker reveals the presence and function of the hyperpolarization-activated cation current I h in peripheral mammalian nerve fibres

Abstract

Electrotonic responses recorded extra- or intracellularly from peripheral 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 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 (I h) in the soma of central mammalian neurones, [8]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 (I h) of peripheral nerve preparations.