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

Chao Tan,Fei Yan,Li-Ping Yao,Wei-Jun Qin,Kun Zhang,Guo-Jun Wu,Jun-Ling Xing,Fei Liu,Jian-Lin Yuan

doi:10.1186/s12894-020-00698-z

Abstract

BackgroundTo investigate the functions of the hyperpolarization-activated cation currents in medium-size dorsal root ganglion cells in a rat model of overactive bladder syndrome.MethodsRats 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.ResultsThe 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.ConclusionsThe 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.

Highlights

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
Did the active characteristics change? Compared with the sham group, the action potentials (AP) amplitude of the medium-size dorsal root ganglia (DRG) neurons in the Overactive bladder syndrome (OAB) group was significantly increased, and the halfwidth decreased from 1.67 ± 0.45 ms to 1.24 ± 0.32 ms (Fig. 1c), the afterhyperpolarization amplitude decreased from 12.45 ± 1.45 mV to 10.37 ± 1.37 mV (Fig. 1c), and the threshold value was significantly less negative (− 31.03 ± 3.24 mV compared to − 38.10 ± 2.31 mV in the control, Fig. 1d) with p values < 0.05 in all cases (OAB vs sham).Taken together, these results indicate that the excitability of the medium-size DRG neurons of the OAB rats was significantly increased
The membrane potential had an obvious depolarization tendency. All these results suggested that the mediumsize L6 DRG cells of the OAB rats had a significantly increased excitability

Summary

Introduction

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. Overactive bladder syndrome (OAB) is characterized by urinary urgency accompanied by frequent urination and nocturia, with or without urinary urge incontinence [1]. Anatomic studies have uncovered that the relevant afferent nerves mainly pass through the pelvic posterior, mainly from the L6 and S1 dorsal root ganglia (DRG) to the spinal cord, to trigger the micturition reflex [3]. The afferent nerves controlling of the urinary bladder include the myelinated Aδ and the unmyelinated C-type fibers [6]. The hyperpolarizationactivated cyclic nucleotide-gated cation (HCN) currents (Ih) have been reported to be expressed by many cell types, such as cardiac pacemaker cells and retinal photoreceptor cells, as well as central and peripheral nerve cells, including DRG cells

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Discussion

Conclusion