Characterization of hyperpolarization-activated current (Ih) in dorsal root ganglion neurons innervating rat urinary bladder.
Afferent pathways innervating the urinary bladder consist of myelinated Adelta-fibers and unmyelinated C-fibers. Normal voiding is dependent on mechanoceptive Adelta-fiber bladder afferents that respond to bladder distention. However, the mechanisms for controlling the excitability of Adelta-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 microm), a small portion (19%) of which were sensitive to capsaicin (1 microM), than in uniformly capsaicin-sensitive small-sized (27.6 +/- 0.5 microm) bladder neurons. In medium-sized bladder neurons, a selective HCN channel inhibitor, ZD7288, dose-dependently inhibited I(h) currents. ZD7288 (10 microM) 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 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 after-hyperpolarization. Thus, it is assumed that I(h) currents could control excitability of mechanoceptive Adelta-fiber bladder afferent neurons, which are usually capsaicin-insensitive and larger in size than capsaicin-sensitive C-fiber bladder afferent neurons.
Masuda
Noriyuki
N
Department of Urology, University of Pittsburgh School of Medicine, PA 15213, USA.
Hayashi
Yukio
Y
Matsuyoshi
Hiroko
H
Chancellor
Michael B
MB
de Groat
William C
WC
Yoshimura
Naoki
N
D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D014554:Urination / Q000502:physiology
D015221:Potassium Channels; D011743:Pyrimidines; C082246:ICI D2788; D002211:Capsaicin