CD4+CD25high+regulatory T cells (Tregs) are considered to be of vital importance for maintaining immunologic self-tolerance and preventing autoimmune diseases. These cells have been found to be deficient in skin lesions and in the peripheral blood of patients with psoriasis.
To investigate the role of Tregs in the pathogenesis of psoriasis and to evaluate the changes in Tregs in relation to the severity and the clinical course of psoriasis.
Immunohistochemistry (CD3, 4, 8, 79 and FOXP3) was performed in 22 psoriatic patients compared to 5 normal controls. Flow cytometry (CD3, 4, 8, 25 and FOXP3) was performed in 18 psoriatic patients and 8 normal volunteers and reverse transcriptase polymerase chain reaction (foxp3 mRNA) was performed in 8 psoriasis patients.
An increase in the FOXP3+ cell fraction was detected in the lesional psoriatic skin irrespective of the severity of psoriasis as compared with the normal skin. However, a decrease in FOXP3+ cells was observed in the samples obtained from psoriasis of 'acute course'. FOXP3+ Treg populations in the blood of the 'acute course' psoriasis was not different compared to that of 'chronic course' psoriasis and normal controls.
The deficiency of FOXP3+ Tregs in the lesional psoriatic skin might be responsible for the exacerbation of psoriasis.
CD4+CD25high+regulatory T cells; FOXP3; Psoriasis
Dilated cardiomyopathy (DCM) is usually an idiopathic disease with a poor prognosis. Hypocalcemia is a rare and reversible cause of DCM. Here, we report a 50-year-old female with DCM, induced by idiopathic hypoparathyroidism, that improved after treatment with calcium.
Cardiomyopathy, dilated; Hypocalcemia; Hypoparathyroidism
Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its prognosis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the colon. Colonoscopic examination revealed a IIa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen revealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant metastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node metastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature.
Colon carcinoma; Signet ring cell carcinoma; Primary carcinoma; Early stage; Endoscopic mucosal resection
We describe a 64-year-old male patient with panhypopituitarism who experienced polymorphic ventricular tachycardia (VT) associated with long QT intervals. The panhypopituitarism developed as a sequelae of radiation therapy administered 20 years prior to his current presentation and was recently aggravated by urinary tract infection with sepsis. In this case, polymorphic VT was resistant to conventional therapy (including magnesium infusion), and QT prolongation and T wave inversion were normalized after the administration of steroid and thyroid hormones. Thyroid hormone is generally known to be associated with torsades de pointes (TdP), but steroid or other hormones may also provoke TdP. Hormonal disorders should be considered as a cause of polymorphic VT with long QT intervals. Some arrhythmias can be life-threatening, and they can be prevented with supplementation of the insufficient hormone.
Tachycardia, ventricular; Torsades de pointes; Hypopituitarism; Radiotherapy
AIM: To investigate the relationship between the function of vagus nerve and peptide YY3-36 and ghrelin levels after subtotal gastrectomy.
METHODS: We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer. All surgeries were performed by a single skilled surgeon. We measured peptide YY3-36, ghrelin, leptin, insulin, growth hormone levels, and body weight immediately before and one month after surgery.
RESULTS: Vagus nerve preservation group showed less body weight loss and less increase of peptide YY3-36 compared with vagotomy group (-5.56 ± 2.24 kg vs -7.85 ± 1.57 kg, P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL, P = 0.021, respectively). Moreover, patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY3-36 level, typically less than 20% [6 (66.7%) vs 0 (0.0%), P = 0.011, odd ratio = 3.333, 95% confidence interval (1.293, 8.591)].
CONCLUSION: Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy, and this phenomenon may be related to the suppressed activity of peptide YY3-36.
Anal cushion; Anal incontinence; Liquids continence test; Wexner score; Hemorrhoidectomy
AIM: To investigate the efficacy of cap-fitted colonoscopy (CFC) with regard to cecal intubation time.
METHODS: Two hundred and ninety-five patients undergoing screening colonoscopy at Gospel Hospital, Kosin University College of Medicine were enrolled in this randomized controlled trial between January and December 2010. Colonoscopies were conducted by a single endoscopist. Patient characteristics including age, sex, body mass index, history of abdominal surgery, quality of preparation, and the presence of diverticulosis were recorded.
RESULTS: One hundred and fifty patients were allocated into a CFC group and 145 into a non-CFC (NCF) group. Cecal intubations were achieved in all patients. Cecal intubation time in the CFC group was significantly shorter than in the NCF group for specific conditions: age ≥ 60 years, prior abdominal surgery, and poor bowel preparation. The number of detected adenomas was higher in the CFC group than in the NCF group (P = 0.040).
CONCLUSION: CFC facilitated shortening of the cecal intubation time in difficult cases, and was more sensitive for detecting adenomas than was NCF.
Colonoscopy; Cap-fitted colonoscopy; Cecal intubation
A 32‐year‐old woman without a remarkable history presented at the emergency department with strangulation of the neck. CT scans of the neck revealed a displaced cricoid fracture. Six days after admission to hospital, hoarseness and dyspnoea disappeared. On the 10th day, the patient was discharged without complications. The traditional treatment guidelines for laryngeal trauma have recommended an early surgical intervention after immediate tracheotomy in cases of displaced fractures of the cricoid cartilage. The patient could be treated successfully through continuous monitoring of airway obstruction without surgical management.
Achalasia is classified into 3 types according to the Chicago classification. The aim of this study was to investigate characteristics and treatment outcomes of 3 achalasia subtypes in Korean patients.
Fifty-five patients diagnosed with achalasia based on conventional or high-resolution esophageal manometry were consecutively enrolled. Their clinical characteristics, manometric, endoscopic and esophagographic findings and treatment responses were analyzed among the 3 subtypes of achalasia.
Of 55 patients, 21 (38.2%) patients had type I, 28 (50.9%) patients had type II and 6 (10.9%) patients had type III. The median follow-up period was 22.4 (interquartile range, 3.6-67.4) months. Type III patients were older than type I and II patients (70.0 vs. 46.2 and 47.6 years, P = 0.023). The width of the esophagus in type I patients was wider with more frequent bird's beak appearance on esophagogram than the other 2 types (P = 0.010 and 0.006, respectively). Of the 50 patients who received the evaluation for treatment response at 3 months, 7 patients (36.8% vs. 26.9%) were treated with pneumatic dilatation and 4 patients (21.1% vs. 15.4%) with laparoscopic Heller's myotomy in type I and II groups, respectively. The treatment responses of pneumatic dilatation and Heller's myotomy in type I group were 71.4 and 50.0% and in type II were 85.7 and 75.0%, respectively, and all 5 patients in type III group showed good response to medical therapy.
Clinical characteristics of 3 achalasia subtypes in Korean patients are consistent with other studies. Treatment outcomes are variable among 3 subtypes.
Esophageal achalasia; Esophageal motility disorders; Manometry
Stress has a deteriorating effect on hippocampal function. It also contributes to symptom exacerbation in many disease states, including overactive bladder and interstitial cystitis/bladder pain syndrome. We investigated the effects of various types of stresses (restraint, noise, and cold) on short-term memory and apoptosis in relation with corticotropin-releasing factor (CRF) expression.
Rats in the restraint stress group were restrained in a transparent Plexiglas cylinder for 60 minutes twice daily. Rats in the noise stress group were exposed to the 120 dB supersonic machine sound for 60 minutes twice daily. Rats in the cold stress group were placed in a cold chamber at 4℃ for 60 minutes twice daily. Each stress was applied for 10 days. A step-down avoidance test for short-term memory, immunohistochemistry for caspase-3 expression, and western blot analysis for Bax and Bcl-2 expressions were conducted.
Latency time was decreased and CRF expression in the hippocampal dentate gyrus and hypothalamic paraventricular nucleus were increased in all of the stress groups. The number of caspase-3-positive cells in the hippocampal dentate gyrus was increased and the expressions of Bax and Bcl2 in the hippocampus were decreased in all of the stress groups.
All of the stress groups experienced short-term memory impairment induced by apoptosis in the hippocampus. The present results suggest the possibility that these stresses affecting the impairment of short-term memory may also induce functional lower urinary tract disorders.
Restrain stress; Noise stress; Cold stress; Short-term memory; Apoptosis
The described oxime-based library protocol provides detailed procedures for the linkage of aminooxy functionality with aldehyde building blocks that result in the generation of libraries of multidentate inhibitors. Synthesis of inhibitors for protein tyrosine phosphatases (PTPs) and antagonists directed against the human tumor susceptibility gene 101 (Tsg101) are shown as examples. Three steps are involved: a) the design and synthesis of aminooxy platforms; b) tethering with aldehydes to form oxime-based linkages with sufficient purity; and c) direct in vitro biological evaluation of oxime products without purification. Each coupling reaction is a) performed in capped microtubes at room temperature; b) diluted for inhibitory evaluation and c) screened with targets in microplates to provide IC50 or Kd values. The synthesis of the aminooxy platforms takes 3–5 days; tethering with the aldehydes takes 24 h; and inhibition assay of enzymes and protein-protein interactions (PPIs) takes 30 min and 2 h respectively.
Oxime; aminooxy platform; multidentate inhibitors; PTP; YopH; PPIs; Tsg101; click chemistry
Sleep disturbances and emotional dysfunction are commonly associated with gastroeophageal reflux disease (GERD). The aims of this study were to evaluate GERD symptoms and disturbance in erosive reflux disease (ERD) and nonerosive reflux disease (NERD) patients, and to compare sleep dysfunction, depressive mood, anxiety and quality of life (QOL) among the control, ERD and NERD patients in Korea.
The Korean subjects were enrolled between 2010 and 2012, classified into 3 groups; the control group with no symptom and normal endoscopic findings, the ERD group with erosive esophagitis and the NERD group with more than one episode of heartburn or acid regurgitation per week, positive response to proton pump inhibitor, and normal endoscopic findings. Questionnaire included GERD symptoms, GERD impact scale (GIS) and daytime pathological sleepiness (Epworth sleepiness scale), sleep dysfunction (Pittsburgh sleep quality index, PSQI), depression and anxiety (Hospital anxiety and depression scale, HADS) and QOL (WHO quality of life scale abbreviated version, WHOQOL-BREF).
A total of 217 subjects were enrolled as follows; control (n = 70), ERD (n = 70) and NERD (n = 77). Impact of symptom of GIS score was higher in the NERD (9.2 ± 0.4) than in the ERD (6.5 ± 0.3) group (P < 0.001). Sleep dysfunctions were more frequent in GERD than the control group (PSQI score [P = 0.021]). Anxiety subscale of HAD score was higher in NERD (7.0 ± 0.5, P = 0.002) and ERD (6.2 ± 0.7, P = 0.004) groups than control (4.3 ± 0.7) group. WHOQOL-BREF scores in NERD (54.9 ± 2.3) and ERD (57.8 ± 2.4) groups were significantly lower than those in the control group (63.8 ± 2.4) (P = 0.002; P = 0.014, respectively).
The patients with NERD than ERD suffered more from the symptoms and disturbance in Korea. Sleep dysfunction and anxiety mood were higher and QOL was decreased in GERD, especially in NERD, suggesting that those factors might affect the severity of NERD.
Emotions; Gastroesophageal reflux; Quality of life; Sleep
Background and Purpose
Sudden cardiac death is one of the leading causes of death in patients with myotonic dystrophy type 1 (DM1). It has been proposed that a prolonged QT interval is associated with sudden cardiac death in several neurological diseases, including multiple system atrophy, idiopathic Parkinson's disease, and diabetic autonomic neuropathy. However, analyses of the corrected QT (QTc) interval in DM1 patients are rare in the literature. The purposes of this study were to determine the association between the QT interval and DM1, and the affecting factors.
Thirty-nine patients diagnosed with DM1 through genetic testing were enrolled. The QTc interval (calculated using Bazett's formula: QTc=QT/√RR) was compared between these patients and 39 normal healthy controls. The clinical and laboratory factors affecting QTc interval in the patient group were investigated.
The QTc interval was significantly longer in the DM1 group (411.2±44.7 msec, mean±SD) than in the normal control group (355.6±20.6 msec). Intragroup analysis revealed that a prolonged QTc interval in DM1 patients was associated with being female and older, having a longer disease duration, and exhibiting abnormal electrocardiography findings.
The higher incidence of sudden cardiac death in the DM1 population is associated with the observed prolonged QTc interval in those patients.
myotonic dystrophy; corrected QT interval; Bazett's formula; sudden cardiac death
There has been no report regarding the regression of Barrett's esophagus (BE) by continuous treatment of proton pump inhibitor (PPI). The aim of this study was to determine the regression rate of BE by PPI and predictable markers related to regression.
Thirty-five patients diagnosed as BE were consecutively enrolled and most of them took continuous PPI. The 25 patients underwent endoscopic surveillance and received biopsy. If the specialized intestinal metaplasia (SIM) was lost at any point of surveillance and did not recur, the case was regarded as the regression group. The proportion of SIM was graded and the mucin phenotype was decided using immunohistochemistry for MUC2, MUC5AC and MUC6. To assess the cell proliferation indexes and the degree of intestinal maturation, immunohistochemistry for Ki67 and CDX2 were performed.
The regression of BE occurred in the 11 (44%) patients. The clinical and demographic factors showed no difference between the regression (n = 11) and persistence group (n = 14). The lower grade of SIM (P < 0.001) and gastric predominant mucin phenotype (P = 0.018) were more frequent, and the number of Ki67 positive cell per gland (P = 0.008) and the mean extent of CDX2 (P = 0.022) were lower in the regression group than in the persistence group.
The regression of BE by PPI treatment was frequent in Korea. The immunohistochemical detection of mucin phenotype, grade of SIM, Ki67 and CDX2 expression in Barrett's mucosa could be useful as a predictable marker for regression of SIM in BE.
Barrett esophagus; Biologic markers; Regression
This study evaluated the effect of Helicobacter pylori eradication on functional dyspepsia (FD), and the relationship between the changes of histological gastritis and FD symptom responses.
A total of 213 FD patients diagnosed by Rome III criteria were consecutively enrolled. H. pylori tests and gastritis grade by the Sydney system were performed before and 1 year after the proton pump based-eradication therapy for 7 days. Serum levels of pepsinogen, and genetic polymorphisms IL-6, IL-8 and IL-10 were investigated.
Total of 91 patients completed the 1 year follow-up. When the response rate of dyspepsia was compared at 1 year between the non-eradicated group (n = 24) and eradicated group (n = 67), each group showed complete response of 62.5% and 62.7%; satisfactory response (≥ 50%) of 0.0% and 19.4%; partial response (< 50%) of 12.5% and 11.9%; and refractory response of 25.0% and 6.0%, respectively (P = 0.015). In addition, the responder group (complete + satisfactory response) at 1 year showed improvement of activity and chronic inflammation in both the antrum and corpus (all P < 0.001). Multivariate analysis showed that H. pylori eradication (OR, 5.81; 95% CI, 1.07-31.59) and symptom improvement at 3 month (OR, 28.90; 95% CI, 5.29-157.82) were associated with the improvement of dyspepsia at 1 year. Among the successfully eradicated FD patients (n = 67), male (P = 0.013) and higher initial BMI (P = 0.016) were associated with the improvement of dyspepsia at 1 year.
H. pylori eradication improved FD symptoms, as well as gastritis at 1 year, suggesting that inflammation mediates FD.
Eradication; Functional dyspepsia; Helicobacter pylori
Thermosensation is mediated by ion channels that are highly temperature-sensitive. Several members of the family of transient receptor potential (TRP) ion channels are activated by cold or hot temperatures and have been shown to function as temperature sensors in vivo. The molecular mechanism of temperature-sensitivity of these ion channels is not understood. A number of domains or even single amino acids that regulate temperature-sensitivity have been identified in several TRP channels. However, it is unclear what precise conformational changes occur upon temperature activation. Here, we used the cysteine accessibility method to probe temperature-dependent conformations of single amino acids in TRP channels. We screened over 50 amino acids in the predicted outer pore domains of the heat-activated ion channels TRPV1 and TRPV3. In both ion channels we found residues that have temperature-dependent accessibilities to the extracellular solvent. The identified residues are located within the second predicted extracellular pore loop. These residues are identical or proximal to residues that were shown to be specifically required for temperature-activation, but not chemical activation. Our data precisely locate conformational changes upon temperature-activation within the outer pore domain. Collectively, this suggests that these specific residues and the second predicted pore loop in general are crucial for the temperature-activation mechanism of these heat-activated thermoTRPs.
Microneedles provide a minimally invasive means to transport molecules into the skin. A number of specific strategies have been employed to use microneedles for transdermal delivery.
The purpose of this study was to investigate the safety of two new digital microneedle devices (Digital Hand® and Digital Pro®; Bomtech Electronics Co., Ltd., Seoul, Korea) for the perforation of skin in skin-hairless-1 mice. This device replaces conventional needles and is designed specifically for intradermal delivery.
We used two newly developed digital microneedle devices to perforate the skin of skin-hairless-1 mice. We conducted a comparative study of the two digital microneedle devices and DTS® (Disk type-microneedle Therapy System; DTS lab., Seoul, Korea). To evaluate skin stability, we performed visual and dermatoscopic inspections, measurements of transepidermal water loss, and biopsies.
The two novel digital microneedle devices did not induce significant abnormalities of the skin on visual or dermatoscopic inspection, regardless of needle size (0.25~2.0 mm). No significant histopathological changes, such as inflammatory cell infiltration, desquamation of the stratum corneum, or disruption of the basal layer, were observed. The digital microneedle devices and microneedle therapy system produced similar results on measures of skin stability.
These two novel digital microneedle devices are safe transdermal drug delivery systems.
Digital; Mesotherapy; Safety; Water loss
Spontaneous reporting systems have several weak points, such as low reporting rates and insufficient clinical information. Active surveillance programs, such as ward rounds and a clinical data repository (CDR), may supplement the weak points of such systems. We developed active surveillance programs and compared them with existing spontaneous reporting.
We collected adverse drug event (ADE) cases, which comprised 1,055 cases of spontaneous reporting, 309 reported by ward rounds, and 229 found using a CDR. The clinical features and causative drugs were evaluated.
Active surveillance programs detected additional serious ADEs compared to those of spontaneous reporting programs. The ADEs identified by CDR (22.9%) were more likely to be classified as "serious" than those reported spontaneously (5.2%) or identified during ward rounds (10.3%). Causative drugs also differed. Opioids, antibiotics, and contrast media were the most common drugs causing ADEs in the spontaneous reporting system, whereas the active surveillance programs identified antibiotics as the most common causative drug. Clinical features also differed. ADEs with gastrointestinal manifestations were reported most frequently by spontaneous reporting programs. ADEs reported from active surveillance more reliably identified events associated with changes in laboratory values, such as hepatobiliary toxicity, hematologic manifestations, and nephrologic manifestations, compared with spontaneous reporting programs.
Our findings suggest that active surveillance programs can supplement spontaneous reporting systems in hospitals. ADEs related to laboratory abnormalities were monitored more closely by active surveillance programs and may be useful for identification of serious ADEs.
Drug toxicity; Spontaneous reporting; Active surveillance
Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA.
Mucinous cystadenocarcinoma; Breast; MUC5; MUC2
The classic Dieulafoy lesion is a minute gastric mucosal defect which bleeds massively from an exposed artery. The typical endoscopic appearance of this lesion is a single, round mucosal defect with an artery protruding from its base in the absence of surrounding ulceration. We encountered an 89-year-old man who developed sudden massive fresh rectal bleeding. The source of hemorrhage was found at colonoscopy after careful irrigation and inspection to be a Dieulafoy lesion situated in rectum. Hemostasis was achieved successfully with epinephrine injection and endoscopic hemostatic clipping.
Hematochezia; Hemostasis; Colonoscopy; Clip
Glycogen rich clear cell carcinoma (GRCC) of the breast is a rare subtype of invasive ductal carcinoma and involves a poor prognosis. In the literature, less than 150 cases have been reported. Many researchers have attempted to characterize GRCC according to electron microscope, flow cytometry, or clinical data. However, an organized study of the immunophenotype of GRCC has yet to be reported.
Materials and Methods
Here, we present three cases of GRCC and their immunohistochemical profiles.
Histologically, all three cases contained periodic acid stain (PAS) positive and d-PAS labile granules in their clear cytoplasm. Case I showed positivity for only estrogen receptor (ER) and c-erbB2. Case II exhibited positivity for progesterone receptor and negativity for ER and c-erbB2. Case III presented with triple negative invasive carcinoma. The expression pattern of E-cadherin was concordant with epidermal growth factor receptor and c-kit, but discordant with ki-67. Among these three cases, p53-positive cases exhibited a low proliferative index (ki-67: 15%), while p53-negative cases showed a high proliferative index (ki-67: 50-60%).
In conclusion, the immunophenotype of GRCC is not uniform, but is similar to that of conventional ductal carcinoma.
Breast; carcinoma; clear cell; glycogen; immunohistochemistry
Bleeding from ectopic varices is rare and accounts for only 1% and 5% of all variceal bleeding. However, once the bleeding starts, it becomes difficult to control and is sometimes fatal. We faced a 65-year-old man with ruptured duodenal varices and injected N-butyl-2-cyanoacrylate into the spurting duodenal varices. As a result, oozing was successfully controlled. Subsequently, the patient remained hemodynamically stable, and no repeat -butyl-2-cyanoacrylate injection was needed. He was finally discharged one week later and has been followed-up for the last one year with no signs and symptoms to suggest any recurrence of bleeding.
Duodenum; Varice; Rupture
Transduction of mechanical stimuli by receptor neurons is essential for senses such as hearing, touch, and pain1–4. Ion channels play a role in neuronal mechanotransduction in invertebrates1; however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, NOMPC, a TRP ion channel, acts as a mechanotransducer in Drosophila melanogaster5 and Caenorhabditis elegans6,7; however, it has no orthologues in mammals. DEG/ENaC family members are mechanotransducers in C. elegans8 and potentially in D. melanogaster9; however, a direct role of its mammalian homologues in sensing mechanical force is not shown. Recently, Piezo1 and Piezo2 were identified as components of mechanically activated (MA) channels in mammals10. Piezos represent an evolutionary conserved family of transmembrane proteins. It is unknown whether Piezos function in mechanical sensing in vivo, and if they do, which mechanosensory modalities they mediate. Here, we study the physiological role of the single Piezo member in D. melanogaster (dpiezo). dpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts [Coste et al., accompanying paper11]. Behavioral responses to noxious mechanical stimuli were severely reduced in dpiezo knockout larvae, while responses to another noxious stimulus or touch were not affected. Knocking down dpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of dpiezo in these same neurons rescued the phenotype of the constitutive dpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a dpiezo dependent, mechanically-activated current. Finally, we found that dpiezo and ppk function in parallel pathways in ppk-positive cells, and that mechanical nociception is abolished in the absence of both channels. These data demonstrate physiological relevance of Piezo family in mechanotransduction in vivo, supporting a role of Piezo proteins in mechanosensory nociception.
Mechanotransduction plays a crucial role in physiology. Biological processes including sensing touch and sound waves require yet unidentified cation channels that detect pressure. Mouse piezo1 (mpiezo1) and mpiezo2 induce mechanically activated cationic currents in cells; however, it is unknown if piezos are pore-forming ion channels or modulate ion channels. We show that Drosophila piezo (dpiezo) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. mpiezo1 assembles as a ~1.2 million-Dalton tetramer, with no evidence of other proteins in this complex. Finally, purified mpiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium red-sensitive ion channels. These data demonstrate that piezos are an evolutionarily conserved ion channel family involved in mechanotransduction.