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- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is known about their possible role in cystitis-associated bladder dysfunction. The present study aimed to determine the functional role of HCN channels in regulating bladder function under inflammatory conditions. Sixty female wild-type C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to experimental and control groups, respectively. Cyclophosphamide (CYP)-induced cystitis models were successfully established in these mice. CYP treatment significantly enhanced HCN channel protein expression and Ih density and significantly altered bladder HCN1 channel regulatory proteins. Carbachol (CCH) and forskolin (FSK) exerted significant effects on bladder ICC-LC [Ca2+]i in CYP-treated wild-type (WT) mice, and HCN1 channel ablation significantly decreased the effects of CCH and FSK on bladder ICC-LC [Ca2+]i in both naive and CYP-treated mice. CYP treatment significantly potentiated the spontaneous contractions and CCH (0.001–10 μM)-induced phasic contractions of detrusor strips, and HCN1 channel deletion significantly abated such effects. Finally, we demonstrated that the development of CYP-induced bladder overactivity was reversed in HCN1 / mice. Taken together, our results suggest that CYP-induced enhancements of HCN1 channel expression and function in bladder ICC-LCs are essential for cystitis-associated bladder hyperactivity development, indicating that the HCN1 channel may be a novel therapeutic target for managing bladder hyperactivity.
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참고문헌 (23)
참고문헌 신청
[학술지
Anderson UA / 2009 / KCNQ currents and their contribution to resting membrane potential and the excitability of interstitial cells of Cajal from the guinea pig bladder / J U
Andersson KE / 2004 / Urinary bladder contraction and relaxation : physiology and pathophysiology / Physiol Rev 84 : 935 ~ 986
Boudes M / 2011 / Functional characterization of a chronic cyclophosphamide-induced overactive bladder model in mice / Neurourol Urodyn 30 : 1659 ~ 1665
Coelho A / 2015 / Urinary bladder inflammation induces changes in urothelial nerve growth factor and TRPV1 channels / Br J Pharmacol 172 : 1691 ~ 1699
Anderson UA / 2009 / KCNQ currents and their contribution to resting membrane potential and the excitability of interstitial cells of Cajal from the guinea pig bladder / J U
Andersson KE / 2004 / Urinary bladder contraction and relaxation : physiology and pathophysiology / Physiol Rev 84 : 935 ~ 986
Boudes M / 2011 / Functional characterization of a chronic cyclophosphamide-induced overactive bladder model in mice / Neurourol Urodyn 30 : 1659 ~ 1665
Coelho A / 2015 / Urinary bladder inflammation induces changes in urothelial nerve growth factor and TRPV1 channels / Br J Pharmacol 172 : 1691 ~ 1699
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