Basic Research - Neurourology & LUTS/BPH & Others(구연) Oral Session6 / Basic Research - non-Cancer (I): Neurourology (O-066) Rm.203 10월 30일(수) 15:00-16:00 사람 전립선 평활근에서 Kv7 이온통로의 분자생물학적 특성 및 기능적 역할 성균관대학교 의과대학 삼성서울병원 비뇨기과학교실 이성원, 채미리, 강수정, 신지민, 최중원 Objectives: Male lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) is driven by increased prostate smooth muscle tone and/or prostatic enlargement. Regulation of prostate smooth muscle tone is an important strategy for medical treatment of voiding symptoms. KCNQ-encoded voltage-gated potassium channels (Kv7) are key regulator of smooth muscle excitability and contractility. Kv7 channel have a specific tissue distribution profiles and pathophysiological role. Loss of function mutations in four of the five Kv7 genes lead to distinct inherited diseases. However, their physiological role in prostatic smooth muscle has yet to be determined. In this study, we examined the molecular expression and physiological roles of Kv7 channels in human prostatic smooth muscle (HPrSM). Methods: Expression of KCNQ1–5 (pore-forming α-subunits) and KCNE 1-5 (β-regulatory subunits) isoforms in HPrSM cells were examined using Real-time PCR. Using the organ bath technique and amphotericin-B perforated patch-clamp electrophysiology, and in situ proximity ligation assay (PLA), physiological roles and properties of Kv7 channel were evaluated. Results: Of the five KCNQ and KCNE subtypes, KCNQ4, KCNQ5 and KCNE4 isoform predominant in HPrSM cells. ML213, an activator of Kv7.2, 7.4 and 7.5, induced concentration-dependent relaxation of NE-induced contraction in HPrSM strips. In electrophysiology studies, ML213 caused a significant increase in the amplitude of whole cell Kv7 currents. The effect was greater potency than retigabine, an activator of Kv7.2-7.5, (ML213: 49%, retigabine: 24%, n=9-11, P<0.01). ML213-induced currents was significantly inhibit by Kv7 channel blocker XE991 (n=9, P<0.01 vs ML213). In current-clamp mode of the perforated patch-clamp, ML213 hyperpolarized cell membrane potential in a manner reversible by XE991. In situ PLA revealed co-localization and expression of heteromeric Kv7.4/Kv7.5 channels in HPrSM cells. Conclusions: We have shown that Kv7 channels are expressed and functionally active in prostatic smooth muscle. These data suggest that Kv7.4 and 7.5 channels play a critical role in the regulation of PrSM tone, and Kv7 channel subtypes might be novel therapeutic targets for treatment of LUTS associated with BPH. keywords : Kv7 channel, Prostatic smooth muscle, LUTS