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The Ca2+-activated monovalent cation selective transient receptor potential melastatin 4 (TRPM4) channel expressed in pancreatic β-cells is implicated in the β-cell function and insulin secretion, but how pharmacological function of TRPM4 channel affects membrane excitability of β-cells remains largely unknown. Here, we report that pharmacological inhibition of TRPM4 by specific inhibitor 9-phenanthrol attenuates electrical activities of pancreatic β-cells. In whole-cell current clamp recordings, 9-phenanthrol results in inhibition of action potential frequency induced by tolbutamide of the INS-1 pancreatic β-cells in a dose-dependent manner with an IC50 value of 14.99 ± 7.93 μmol·L-1. Similarly, 9-phenanthrol also inhibited action potential firing in INS-1 cells stimulated by current injection. Further recordings of β-cells demonstrate the significant inhibitory effects on action potential peak and action potential amplitude by 9-phenanthrol. Taken together, our results show the involvement of TRPM4 channel function in pancreatic β-cells depolarization and action potential, it provides pharmacological experimental methods and theoretical support for the study of TRPM4 channel in pancreatic β-cells.
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Objective To summarize the clinical,radiographic and genetic features of a family with metatropic dysplasia,in order to improve the level of understanding and diagnosis of this disease.Methods The proband,a one-year old boy,was diagnosed as metatropic dysplasia.His mother was 26 years old with mildly phenotype.Their clinical features and bone X-ray findings were analyzed.The DNA samples of the proband and his parents were collected.The coding exons and flanking introns regions of transient receptor potential vanilloid 4 (TRPV4) gene were amplified by polymerase chain reaction (PCR) and analyzed by DNA automatic detector.The pathology,diagnosis,treatment and prognosis were expounded.Results The symptoms of the boy were characterized by short extremities,a short trunk with progressive kyphoscoliosis,and craniofacial abnormalities that include a prominent forehead,midface hypoplasia,and a squared-off jaw.His motor development was slightly delayed.Mental development was normal.Bone X ray of the boy showed platyspondyly and severe metaphyseal enlargement with shortening of long bones and irregularities and delayed ossification of epiphysis.The patient and his mother were heterozygous for the nucleotide substitutions c.2396 ＞ T (p.P799L) in TRPV4 gene.Conclusions The patient and his mother with metatropic dysplasia were diagnosed with TRPV4 gene analysis.The patient showed typical clinical features.His mother was mild.Metatropic dysplasia had significantly clinical heterogeneity.Gene analysis is helpful for the diagnosis.
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Objective To explore the basic medical mechanism of XinBao pill on electrophysiological characteristics of hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), and illustrate the mechanism of its therapeutical effect on bradycardia.Methods Human HCN4 mRNA was injected into the Xenopus laevis oocytes, after incubated for 2 ~3 days, channel current properties of HCN4 perfused with 40 mg/L XinBao Pill were observed by double electrode voltage clamp technique.Results At-90mV test potential, compared with control group (no XinBao pill), HCN4 channel peak current and tail current in 40 mg/L XinBao pill group had obvious changes, and V1/2 from ( -103.61 ±3.57)mV to ( -106.42 ±5.33)mV in XinBao pill group, from( -81.11 ±4.26)mV to( -86.36 ±7.44)mV in control group.The values of k from (15.15 ±2.23)mV to (17.33 ±3.58) mV in XinBao pill group, from(11.78 ±0.85)mV to(12.39 ±1.51)mV in control group(n=10).At test potential -90 mV, 40 mg/L XinBao pill perfusion fluid decreased the instantaneous current of(0.15 ±0.24)%, the EC50 was (30.8 ±4.8)mg/L (n=8).At test potential-140 mV~-100 mV level, 40 mg/L XinBao pill group increased the channel activation time constant compared with control group[(226.73 ±31.36)ms vs(143.67 ± 21.44)ms;-140 mV,n=10,P<0.05].40 mg/L XinBao pill group increased the channel deactivation time constant compared with control group [(1293.53 ±95.02)ms vs (647.12 ±61.35)ms;-140 mV,n=10,P<0.05].Conclusion The XinBao pill enhances the instantaneous current of HCN4 in a concentration-dependent manner, and extents channel activation and deactivation processes.
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PURPOSE: Single incision laparoscopic cholecystectomy (SILC) is a widely used method of performing cholecystectomy. A common technique used in SILC is a 3-channel method. However, exposure of Calot's triangle is limited in conventional 3-channel SILC. Therefore, we herein report the adequacy and feasibility of 4-channel SILC using a snake retractor. METHODS: Four hundred and fifteen SILC cases were performed between April 2010 and February 2013. We performed 326 SILC cases between April 2010 and September 2012 using the 3-channel method. We introduced a snake retractor for liver traction in October 2012, and 89 cases of 4-channel SILC using snake retractor have been performed since. RESULTS: Thirty patients (9.2%) in the 3-channel SILC group, and 23 patients (25.8%) in the 4-channel SILC group, were treated with percutaneous transhepatic gallbladder drainage insertion because of acute inflammation of the gallbladder (GB) before operation (P < 0.001). The mean operating time was 53.0 +/- 25.8 minutes in the 3-channel SILC group and 51.9 +/- 18.6 minutes in the 4-channel SILC group (P = 0.709). In the 3-channel SILC group, mean hospital stay was 3.0 +/- 3.3 days whereas it was 2.6 +/- 0.9 days in the 4-channel SILC group (P = 0.043). There were a total 9 cases (2.1%) of additional port usages, 6 cases (1.8%) in the 3-channel SILC group and 3 cases (3.4%) in the 4-channel SILC group (P = 0.411), due to cystic artery bleeding and bile leakage from gallbladder bed, but there were no open conversions. CONCLUSION: Benign diseases of the GB can be operated on using SILC with the 4-channel method using a snake retractor.
Subject(s)
Humans , Arteries , Bile , Cholecystectomy , Cholecystectomy, Laparoscopic , Drainage , Gallbladder , Hemorrhage , Inflammation , Laparoscopy , Length of Stay , Liver , Snakes , TractionABSTRACT
Objective To study the effects of the antiarrhythmic drugs of propafenone, amiodarone and dilthiazem on c-type Kv1. 4 channels in Xenopus laevis oocytes with two-electrode voltage-clamp technique. Methods Defolliculated oocytes ( stage Ⅴ - Ⅵ) had transcribed cRNAs of ferret Kv1. 4△N channels injected. The oocytes were continuously perfused with control solution or propafenone, amiodarone and dilthiazem under monitoring of software of Clampfit v 9. 0. Results All of the three drugs blocked ferret Kv1. 4△N channel in voltage-, frequency- and concentration-dependent manners. The values of IC50 (50%inhibiting concentration ) of propafenone, amiodarone and dilthiazem were ( 103.4± 2. 2 ) μ mol/L,(501.22 +5.9) μmol/L and (353.62 +9.9) μmol/L, respectively. The currents under the actions of propafenone , amiodarone and dilthiazem were decreased to 41%, 32% and 21% of control group, respectively. Propafenone (100μ mol/L), Amiodarone (500μmol/L), dilthiazem (350μmol/L) inhibited currents to (54. 6 + 1.9 ) %, ( 46. 3 + 3.5 ) %, ( 52. 8 ± 2. 8 ) % of control group in voltage-dependent blockage. Conclusions The results suggested that all the three drugs blocked the kv1. 4△N channel in the open state. The three drugs block the kv1. 4△N channel maybe had the similiar effects in some respects, but each had its unique characteristics.
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Tetrodotoxin (TTX) is a highly potent neurotoxin that blocks the action potential by selectively binding to voltage-gated sodium channels (Na v). The skeletal muscle Na v (Na v1.4) channels in most pufferfish species and certain North American garter snakes are resistant to TTX, whereas in most mammals they are TTX-sensitive. It still remains unclear as to whether the difference in this sensitivity among the various vertebrate species can be associated with adaptive evolution. In this study, we investigated the adaptive evolution of the vertebrate Na v1.4 channels. By means of the CODEML program of the PAML 4.3 package, the lineages of both garter snakes and pufferfishes were denoted to be under positive selection. The positively selected sites identified in the p-loop regions indicated their involvement in Na v1.4 channel sensitivity to TTX. Most of these sites were located in the intracellular regions of the Na v1.4 channel, thereby implying the possible association of these regions with the regulation of voltage-sensor movement.
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The main purpose of this article is to determine a method of supporting the sympathetic skin response (SSR) as a sensitive clinical test. Using a non-invasive technique the SSRs are simultaneously recorded by 4 channel EMG machine. Thirty adults (10 women and 20 men, aged 19 to 46 years), normal and healthy, participated in this experiment. Not only did the latencies recorded on both palms respond faster than those on both soles, but the amplitudes measured on the palms were also higher. From these observations, one is bound to conclude that the SSR is not a segmental response but a long systemic response. More than two channel EMG recordings are desirable to see whether or not there is a lesion in any part of the SSR's pathway. Comparing the SSRs made both on the palms and soles simultaneously is recommendable in order to increase the its sensitivity.