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

Afferent pathways innervating the urinary bladder consist of myelinated Aδ-fibers and unmyelinated C-fibers. Normal voiding is dependent on mechanoceptive Aδ-fiber bladder afferents that respond to bladder distention. However, the mechanisms for controlling the excitability of Aδ-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 I h 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 μm), a small portion (19%) of which were sensitive to capsaicin (1 μM), than in uniformly capsaicinsensitive small-sized (27.6 ± 0.5 μm) bladder neurons. In medium-sized bladder neurons, a selective HCN channel inhibitor, ZD7288, dose-dependently inhibited I h currents. ZD7288 (10 μM) also increased the time constant of the slow depolarization phase of spike afterhyperpolarization from 91.8 to 233.0 ms. These results indicate that I h 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 afterhyperpolarization. Thus, it is assumed that I h currents could control excitability of mechanoceptive Aδ-fiber bladder afferent neurons, which are usually capsaicininsensitive and larger in size than capsaicin-sensitive C-fiber bladder afferent neurons. Dorsal root ganglion Urinary bladder I h HCN channel ZD7288 Hyperpolarization B R A I N R E S E A R C H 1 0 9 6 ( 2 0 0 6 ) 4 0 -5 2 ava i l a b l e a t w w w. s c i e n c e d i r e c t . c o m w w w. e l s ev i e r. c o m / l o c a t e / b r a i n r e s