Basic Research - Infertility & Sexual Dysfunction(구연) (NP-009) 음경해면체 평활근에서 Kv7 채널의 특성 및 기능적 역할 성균관대학교 의과대학 삼성서울병원 비뇨기과학교실 정재동, 채미리, 강수정, 이종훈, 성현환, 이성원 Objectives KCNQ-encoded voltage-gated potassium channels (Kv7) have recently been identified as key regulator of vascular and non-vascular smooth muscle tone. Kv7 channel subtypes (Kv7.1-Kv7.5) have a specific tissue distribution and pathophysiological role. Loss of function mutations in four of the five KV7 genes lead to distinct inherited diseases. such as cardiac arrhythmias, epilepsy and sensorineuronal deafness. However, their physiological role in corporal smooth muscle (CSM) remains to be fully elucidated. In this study, we examined the molecular expression and functional role of Kv7 channels in corporal smooth muscle. Materials & Methods Expression of KCNQ isoforms in corporal smooth muscle (CSM) cells was examined using RT-PCR. Functional responses to Kv7 channel modulators were evaluated in normal and diabetic (DM) rabbit corporal smooth muscle (CSM) tissue. Isolated CSM strips were mounted in an organ-bath system, and the relaxation effects of the following Kv7 channel subtype selective activators: ML213 (Kv7.2/Kv7.4channels), ML277 (Kv7.1) and ICA 069673 (Kv7.2/7.3), Flupirtine (Kv7.2–7.5 channels) were evaluated by cumulative addition to strips pre-contracted with10-5 M phenylephrine (PE). Results Of the five KCNQ subtypes, the transcripts for KCNQ1, KCNQ3-KCNQ5 were detected in human corpus cavernosum smooth muscle cells. In functional studies, Flupirtine, ML277 and ML213 produced a concentration-dependent relaxation of PE-induced contractions, with potencies of ML213> Flupirtine> ML277 (at 30 µM, ML213: 100.9±7.7%, Flupirtine: 59.4±14.3%, ML277: 29.1±1.8%, n=8, p<0.05). Whereas ICA 069673 was effective at 100 µM (42.3±8.2% at 100 µM, n=8, p<0.05). The effects of ML213 was attenuated by pre-incubation with 1 µM XE991 (Kv7.1–7.5 channel blocker) (n=8, p<0.05), which in turn confirmed Kv7 channels selectivity. Moreover, ML213 also induced concentration-dependent relaxation in CSM strips from diabetic rabbit, with similar potency in normal rabbit. Conclusions These data suggest that Kv7channels, most probably Kv7.4 channels play a role in erectile function and might be a novel therapeutic target for treatment of erectile dysfunction. keywords : Kv7channel, KCNQ, corpus cavernosum, ED