Hyperpolarization-Activated Cation Current In Medium-Sized DRG Neurons Contributed To Overactive Bladder Of The Rat

Obs jects:To investigate the role of hyperpolarizationactivated cyclic nucleotide-gated cation currents(I_h)in medium-sized neurons from dorsal root ganglia(DRG)in contributing overactive bladder(OAB)and related mechanisms.Methods:SD rats were made into OAB models and were verified by urine dynamic flow monitoring.Urinary dynamic parameters were measured,as well as the I_h current density of L6 DRG medium-sized neurons was studied by whole-cell patch clamp.Specific inhibitor of I_h current ZD7288 was applied by intrathecal injection on the L6 DRG.Then the role of ZD7288 on I_h current and urinary dynamic parameters was investigated.Results:(1)Bladder weight significantly increased in the OAB group(p<0.01),and Intrathecally injection of ZD7288(2uM)for 7 days can successfully block the increased bladder weight.(2)Compared to sham group,micturition parameters have changed in OAB rats,micturition intervals became much shorter;micturition volumes became much lesser,and micturition times became much longer.However,ZD7288 can reverse the changed micturition parameters.These changed micturition parameters could be reversed by ZD7288(3)The excitability of medium-sized neurons enhanced significantly in the OAB group,for example,the amplitude of action potential(AP),the numbers of APs which was induced by injected current(500 pA)increased dramatically;moreover,the half-width,threshold,after hyperpolarization potential(AHP),rheobase and ?value were both decreased significantly.However,the excitability of medium-sized neurons was inhibited apparently by ZD7288.(4)The I_h density of medium-sized neurons enlarged a lot in the OAB rats,and was abolished completely by ZD7288.Conclusion:The enlarged I_h density leaded to the higher excitability in medium-sized neurons of OAB rat's DRG.Symptoms of OAB rats were obviously improved whenI_h current density was reduced.It was suggested that the increased I_h density in medium-sized neurons of DRG played an important role in OAB formation.