Characterization of hyperpolarization-activated current (Ih) in dorsal root ganglion neurons innervating rat urinary bladder

Afferent pathways innervating the urinary bladder consist of myelinated A delta-fibers and unmyelinated C-fibers. Normal voiding is dependent on mechanoceptive A delta-fiber bladder afferents that respond to bladder distention. However, the mechanisms for controlling the excitability of A delta-fiber bladder afferents are not fully understood. We therefore used whole cell patch-clamp techniques to investigate the properties of hyperpolarization-activated, cyclic nucleotide-gated (HCN) currents (I-h) in dorsal root ganglion (DRG) neurons innervating the urinary bladder of rats. The neurons were identified by axonal tracing with a fluorescent dye, Fast Blue, injected into the bladder wall. Hyperpolarizing voltage step pulses from -40 to -130 mV produced voltage- and time-dependent inward Ih currents in bladder afferent neurons. The amplitude and current density of I-h at a holding potential of -130 mV was significantly larger in medium-sized bladder afferent neurons (diameter: 37.8 +/- 0.3 mu m), a small portion (19%) of which were sensitive to capsaicin (1 mu M), than in uniformly capsaicin-sensitive small-sized (27.6 +/- 0.5 mu m) bladder neurons. In medium-sized bladder neurons, a selective HCN channel inhibitor, ZD7288, dose-dependently inhibited Ih currents. ZD7288 (10 mu M) also increased the time constant of the slow depolarization phase of spike after-hyperpolarization from 91.8 to 233.0 ms. These results indicate that Ih currents are predominantly expressed in medium-sized bladder afferent neurons innervating the bladder and that inhibition of I-h currents delayed recovery from the spike after-hyperpolarization. Thus, it is assumed that I-h currents could control excitability of mechanoceptive A delta-fiber bladder afferent neurons, which are usually capsaicin-insensitive and larger in size than capsaicin-sensitive C-fiber bladder afferent neurons, (c) 2006 Elsevier B.V. All rights reserved.