Hyperpolarization-activated cation currents in medium-size dorsal root ganglion cells are involved in overactive bladder syndrome in rats.

ABSTRACT

BACKGROUND: To investigate the functions of the hyperpolarization-activated cation currents in medium-size dorsal root ganglion cells in a rat model of overactive bladder syndrome. METHODS: Rats with OAB were screened using a urodynamic testing device. The whole-cell patch clamp technique was used to investigate changes in excitability and hyperpolarization-activated cation current (Ih) of medium-size cells in the L6 dorsal root ganglia (DRG) of the OAB rats. Intrathecal injection of the specific Ih inhibitor ZD7288 was used to investigate changes of voiding function and Ih of medium-size cells in the L6 DRG. RESULTS: The urinary bladder weight of the OAB rats was significantly increased (p < 0.01); However, 7 days after intrathecally administration of ZD7288 (2 µM), the weight of rat bladder was significantly reduced (p < 0.01). The excitability of the medium-size cells in the L6 DRG of the OAB rats was significantly increased, and the number of action potentials elicited by a 500 pA stimulus was also markedly increased. Furthermore, ZD7288 significantly reduced the excitability of the medium-size DRG cells. The medium-size cells in the DRG of the OAB rats had a significantly increased Ih current density, which was blocked by ZD7288. CONCLUSIONS: The Ih current density significantly increased in medium-size cells of the L6 DRG in the OAB model. A decrease of the Ih current was able to significantly improve the voiding function of the OAB rats, in addition to lowering their urinary bladder weight. Our finding suggested that the observed increase of Ih current in the medium-size DRG neurons might play an important role in the pathological processes of OAB.