Basic Research - Infertility & Sexual Dysfunction(구연) (E-021) 새로운 Kv7 채널 활성제 URO-K가 음경해면체 평활근 긴장도 조절에 미치는 영향 성균관의대 삼성서울병원 비뇨기과학교실¹, 전북대학교 의과대학 비뇨기과학교실², 이성원¹, 채미리¹, 신지민¹, 한덕현¹, 성현환¹, 박종관² Objectives: KCNQ-encoded voltage-gated potassium channels (Kv7) play an important role in the regulation of vascular and non-vascular smooth muscle tone. Kv7 dysfunction are involved in the pathogenesis of hypertension and overactive bladder, as well as being implicated in other smooth muscle disorders. Kv7 channels are an important therapeutic target for the treatment of non-neuronal, smooth muscle diseases. We have recently shown that Kv7.4 channel subtype was predominantly expressed in corporal smooth muscle and pharmacological subtype-selective activation of Kv7 channels induced the relaxation of erectile tissue. In this study, we investigated the effect of a newly synthesized compound URO-K, Kv7 channel openers, on corporal smooth muscle. Materials & Methods: Functional response to URO-K was evaluated in rabbit CSM tissue. Isolated CSM strips were mounted in an organ-bath system, and the relaxation effects of URO-K was evaluated by cumulative addition to strips pre-contracted with phenylephrine (PE). Kv7 currents and membrane potential were recorded in human CSM cells using an amphotericin-B perforated patch-clamp technique. Results: URO-K produced a concentration-dependent relaxation of PE-induced contractions (7.4±1.2% at 0.1 μM, 20.4±2.6% at 1 μM, 47.3±4.6% at 3 μM, 84.0±3.3% at 10 μM, 102.1±3.8% at 30 μM, and 109.0±3.6% at 100 μM, n=14). The effect of URO-K was attenuated by pre-incubation with 1 µM XE991 (Kv7.1–7.5 channel blocker) (n=8, p<0.05). Whereas different potassium channel inhibitors (TEA, 4-AP, iberiotoxin) did not altered the relaxant effects of URO-K. In addition, removal of the endothelium from the CSM did not affect the relaxation effect of URO-K. In electrophysiology studies, URO-K significantly increases the Kv7 currents in a concentration-dependent manner, with an EC50 value of 113.0 nM. The subsequent addition of XE991 completely inhibited the URO-K-induced currents (n=8, p<0.05 vs. URO-K). URO-K also hyperpolarized the CSM cell membrane potential (n=12, P<0.05). URO-K-induced CSM cell membrane hyperpolarization was fully reversible by washout of URO-K or XE991. Conclusions: These results show that URO-K leads to an endothelium-independent relaxation of erectile tissue by enhancing the activity of Kv7.4 channels. Thus, URO-K might be a novel therapeutic candidate for treatment of erectile dysfunction. keywords : Kv7.4channel, corpus cavernosum, Erectile dysfunction