ABSTRACT
KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50 , the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the βancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQspecific agonist in the tissue.
ABSTRACT
KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50 , the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the βancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQspecific agonist in the tissue.
ABSTRACT
PURPOSE: To assess the sensitivity, specificity, and diagnostic accuracy of individual contrast-enhanced helical CT findings of acute appendicitis. MATERIALS AND METHODS: We retrospectively reviewed the appendiceal helical CT scans, obtained after intravenous contrast administration (abdomen; 7-mm collimation, abdominopelvic junction; 5-mm collimation), of 50 patients with surgically proven acute appendicitis and 112 with alternative diagnoses. The following parameters were analysed by three radiologists: enlarged appendix (> 6 mm in diameter), appendiceal wall thickening, appendiceal wall enhancement, no identification of the appendix, appendicolith(s), (appendiceal) intraluminal air, (appendiceal) intraluminal air extraluminal air, periappendiceal fat stranding, extraluminal fluid, phlegmon, abscess, lymphadenopathy, terminal ileal wall thickening, focal cecal apical thickening, focal colonic wall thickening, and segmental colonic wall thickening. RESULTS: The CT findings of acute appendicitis that statistically distinguished it from alternative diagnoses were an enlarged appendix (sensitivity; 92%, specificity; 93%, diagnostic accuracy; 93%), appendiceal wall thickening (for these three parameters: 68%, 96% and 88%, respectively), periappendiceal fat stranding (90%, 79%, 82%), appendiceal wall enhancement (72%, 86%, 82%), appendicolith (16%, 100%, 74%), and focal cecal apical thickening (14%, 100%, 74%) (for each, p < 0.05). CONCLUSION: On thin-section contrast-enhanced helical CT, an enlarged appendix and periappendiceal fat stranding were found in 90% or more patients with acute appendicitis. Appendiceal wall thickening and enhancement were clearly demonstrated and significant findings for diagnosis. Less common but specific findings include appendicolith, focal cecal apical thickening and intramural air, can also help us establish a diagnosis of acute appendicitis.