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

Abstract

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 (I h) of medium-size cells in the L6 dorsal root ganglia (DRG) of the OAB rats. Intrathecal injection of the specific I h inhibitor ZD7288 was used to investigate changes of voiding function and I h 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 I h current density, which was blocked by ZD7288. Conclusions The I h current density significantly increased in medium-size cells of the L6 DRG in the OAB model. A decrease of the I h 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 I h current in the medium-size DRG neurons might play an important role in the pathological processes of OAB.

Keywords

• Overactive bladder
• I h
• Dorsal root ganglion
• Hyperpolarization
• ZD7288