[Intervention effect of Erchen Decoction on methionine and choline deficient diet-induced non-alcoholic steatohepatitis in mice].

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD＿L, 6 g·kg~(-1)), medium-dose ECD group(ECD＿M, 12 g·kg~(-1)), and high-dose ECD group(ECD＿H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1ß, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1ß in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD＿M and ECD＿H groups were significantly decreased, and the AST level in the ECD＿L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1ß, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD＿H group. The mRNA expressions of FASN, MCP-1, and IL-1ß in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD＿M and ECD＿H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD＿M and ECD＿H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.

Cell Division Cycle Associated Genes as Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma.

With high mortality and poor prognosis, hepatocellular carcinoma (LIHC) has become the fourth leading cause of cancer-related deaths worldwide. Most of the LIHC patients missed the best treatment period because of the untimely diagnosis. For others, even if they are temporarily cured, they have to face a very low prognostic survival rate and a very high risk of recurrence. Based on the characteristics of abnormal proliferation and uncontrolled growth of tumor cells. Cell Division Cycle Associated (CDCA) family genes, which are responsible for regulating the cell cycle and proliferation, were selected as our research object to explore the mechanism of hepatocarcinogenesis. To this end, we investigated the expression profiles of CDCA family genes in LIHC and corresponding normal tissues, and the effect of CDCAs expression on the survival of prognosis and immune cell infiltration through bioinformatics analysis methods and the publicly accessible online databases. In addition, we also analyzed the expression correlation of CDCAs and screened the neighboring genes related to functional CDCAs. The results revealed that the expression levels of CDCA1/3/5/8 were significantly increased in LIHC, regardless of stage, sex, race, drinking behavior, and other clinical factors. CDCAs expression was significantly correlated with poor prognosis and was positively correlated with the infiltration of dendritic cells, B cells, and macrophages. We also found that the most relevant neighboring genes to CDCAs in LIHC were SGO2, NDC80, BIRC5, INCENP, and PLOD1. In general, our work suggests that CDCA1/3/5/8 has the potential to be a diagnostic gene in hepatocarcinogenesis and prognostic biomarkers for LIHC patients.

Double-Constraint Inpainting Model of a Single-Depth Image.

In real applications, obtained depth images are incomplete; therefore, depth image inpainting is studied here. A novel model that is characterised by both a low-rank structure and nonlocal self-similarity is proposed. As a double constraint, the low-rank structure and nonlocal self-similarity can fully exploit the features of single-depth images to complete the inpainting task. First, according to the characteristics of pixel values, we divide the image into blocks, and similar block groups and three-dimensional arrangements are then formed. Then, the variable splitting technique is applied to effectively divide the inpainting problem into the sub-problems of the low-rank constraint and nonlocal self-similarity constraint. Finally, different strategies are used to solve different sub-problems, resulting in greater reliability. Experiments show that the proposed algorithm attains state-of-the-art performance.

Application of ultrasonography guided water injection for insertion of naso-jejunal tubes / 中华护理杂志

Objective To examine the effects of application of ultrasonography guided water injection for inser-tion of naso-jejunal tubes. Methods Hospitalized patients in ICU who needed naso-jejunal tubes were recruited from one tertiary hospital in Beijing from November 2016 to April 2017. Ultrasonography guided water injection was used to assist insertion of naso-jejunal tubes. Meanwhile,we conducted semi-structured interviews to learn feel-ings and suggestions from the patients. Results A total of 40 patients were included in this study,37 patients (92.5%) were successfully inserted with the tubes at the first attempt. The duration of insertion of naso-jejunal tubes was 25 (20,38.75) min. Conclusion Ultrasonography guided water injection is a simple and convenient method to guide the placement of naso-jejunal tubes for critical ill patients,which provides guarantee for early en-teral nutrition.

Effect of suppressing apoptosis signal regulating kinase 1 on GFAP and vimentin expression and hindlimb mobility in rats after spinal cord injury / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of suppressing apoptosis signal regulating kinase 1 (ASK1) on glial fibrillary acidic protein (GFAP) and vimentin expressions at the injury site and on hindlimb mobility in rats after spinal cord injury (SCI).</p><p><b>METHODS</b>The rat models of SCI were established by extradural compression of the spinal cord using an aneurysm clip. The injured rats were treated with normal saline (model group), ASK1 specific inhibitor thioredoxin (Trx group), or ASK1 monoclonal antibody (Anti-ASK1 group), and the rats receiving a sham operation underwent laminectomy without SCI. The expression of GFAP and vimentin were detected by Western blotting and immunofluorescence assay at 1, 7, 14 and 28 days after SCI. The motion function of the hindlimbs of the injured rats was assessed with Basso Beattie Bresnahan (BBB) scores, and somatosensory-evoked potentials (SEP) and motor-evoked potentials (MEP) were determined to examine the electrophysiological changes.</p><p><b>RESULTS</b>At 1 day after SCI, the expressions of GFAP and vimentin showed no significant differences among the groups; at 7, 14 and 28 days after SCI, GFAP and vimentin expressions significantly increased in Trx and Anti-ASK1 groups compared with those in the model group (P<0.01). The BBB scores showed no significant differences among the groups at 1, 7 and 14 days after SCI, while at 28 days, the BBB scores in Trx and Anti-ASK1 groups were significantly higher than those in the model group (P<0.01). At 28 days after SCI, the latent period of SEP and MEP decreased and the amplitude increased significantly in Trx and Anti-ASK1 groups compared with that in the model group (P<0.01).</p><p><b>CONCLUSION</b>Blocking ASK1 can inhibit the expression of GFAP and vimentin in glial scars and improve the outcomes of hindlimb mobility in rats after SCI.</p>

Novel method for culturing Schwann cells from adult mouse sciatic nerve in vitro.

Schwann cells (SCs) are important in the recovery of peripheral nerve injury and are valuable cells for the tissue engineering of artificial neurons. Clinical applications that require pure SCs in large quantities are limited since human and mouse SCs do not attach well to the wall of the culture dish and have low proliferative potential. To obtain high quantities of highly pure SCs, we developed a new method for culturing SCs from the mouse sciatic nerve in vitro. Approximately 1.5 cm of the bilateral sciatic nerve of a c57 adult mouse was surgically removed and pre-cultured in DMEM containing either 10% FBS or growth factors. One week later, the in vitro SC culture was observed using light microscopy following enzyme digestion. Cell numbers and cell attachment were examined. The purity of the SCs was determined using s100ß and p75NTR staining. Sciatic nerves that had not been pre-cultured were used as the control group. When the excised tissue was pre-cultured in vitro, high yields of SCs were obtained. The SCs were more likely to adhere and the purity was approximately 98% at the p1 generation following simple purification steps, which was significantly higher than the purity obtained from the control group. The pre-culturing of the sciatic nerve prior to in vitro tissue culturing significantly increased the quantity and quality of the SCs.

Discovery of ((1S,3R)-1-isopropyl-3-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-ylamino)cyclopentyl)(4-(5-(trifluoromethyl)pyridazin-3-yl)piperazin-1-yl)methanone, PF-4254196, a CCR2 antagonist with an improved cardiovascular profile.

We describe the systematic optimization, focused on the improvement of CV-TI, of a series of CCR2 antagonists. This work resulted in the identification of 10 (((1S,3R)-1-isopropyl-3-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-ylamino)cyclopentyl)(4-(5-(trifluoromethyl)pyridazin-3-yl)piperazin-1-yl)methanone) which possessed a low projected human dose 35-45mg BID and a CV-TI=3800-fold.

Transperitoneal versus retroperitoneal laparoscopic radical nephrectomy: A comparison of clinical outcomes / 第二军医大学学报

Objective To compare clinical outcomes of transperitoneal and retroperitoneal laparoscopic radical nephrectomy for renal cell carcinoma (RCC) and to identify the indicators for each approach. Methods A total of 258 patients underwent transperitoneal (n = 116) or retroperitoneal (n = 142) laparoscopic radical nephrectomy for RCC. The operation time, blood loss during operation, fasting period after surgery and hospital stay were compared between the two groups. Results The operation timewas 80-315 min (a mean of [167 ±66. 8] min) for transperitoneal approach and 85-280 min (a mean of [152± 48.8] min) for retroperitoneal approach (P = 0. 034). The blood loss was 50-1,000 ml (a mean of [181±140. 4] ml) for transperitoneal approach and 50-800 ml (a mean of [171 ± 132. 9] ml) for retroperitoneal approach(P = 0. 544). The fasting period of surgery was 1-5 d (a mean of [2. 8±1. 3] d) for transperitoneal approach and 1-5 d (a mean of [2. 9 ±1. 2] d) for retroperitoneal approach(P = 0. 801). The hospital stay was 3-9 d (a mean of [6. 6±1. 5] d) for transperitoneal approach and 3-8 d (a mean of [6. 5±1. 6] d) for retroperitoneal approach(P = 0. 477). Conclusion Transperitoneal and retroperitoneal approaches both can yield satisfactory surgical outcomes in laparoscopic radical nephrectomy. The transperitoneal approach is suitable for tumors with a larger size.

Transperitoneal versus retroperitoneal laparoscopic radical nephrectomy: A comparison of clinical outcomes / 第二军医大学学报

To compare clinical outcomes of transperitoneal and retroperitoneal laparoscopic radical nephrectomy for renal cell carcinoma (RCC) and to identify the indicators for each approach. Methods A total of 258 patients underwent transperitoneal(n=116) or retroperitoneal (n=142) laparoscopic radical nephrectomy for RCC. The operation time, blood loss during operation, fasting period after surgery and hospital stay were compared between the two groups. Results The operation time was 80-315 min(a mean of [167±66.8] min) for transperitoneal approach and 85-280 min(a mean of [152± 48.8] min) for retroperitoneal approach (P=0.034). The blood loss was 50-1,000 ml (a mean of [181±140.4] ml) for transperitoneal approach and 50-800 ml(a mean of [171±132.9] ml) for retroperitoneal approach(P=0.544). The fasting period of surgery was 1-5 d (a mean of [2.8±1.3] d) for transperitoneal approach and 1-5 d (a mean of [2.9±1.2] d) for retroperitoneal approach(P=0.801). The hospital stay was 3-9 d (a mean of [6.6±1.5] d) for transperitoneal approach and 3-8 d (a mean of [6.5±1.6] d) for retroperitoneal approach(P = 0. 477). Conclusion Transperitoneal and retroperitoneal approaches both can yield satisfactory surgical outcomes in laparoscopic radical nephrectomy. The transperitoneal approach is suitable for tumors with a larger size.

Ciliary neurotrophic factor-coated polylactic-polyglycolic acid chitosan nerve conduit promotes peripheral nerve regeneration in canine tibial nerve defect repair.

A variety of nerve conduits incorporated with chemical and biological factors have been developed to further stimulate nerve regeneration. Although most of the nerve guides in studies are basically limited to bridge a short gap of nerve defect in rat models, it is vital to evaluate effects of conduits on nerve regeneration over distance greater than 20 mm, or more clinically relevant nerve gap lengths in higher mammals. In this study, a poly(lactide-co-glycolide) (PLGA) nerve conduit, treated with pulsed plasma and coated with ciliary neurotrophic factor (CNTF) as well as chitosan, was used to repair 25-mm-long canine tibial nerve defects in eighteen cross-bred dogs. The canines were randomly divided into three groups (n = 6), a 25-mm segment of the tibial nerve was removed and replaced by a PLGA/chitosan-CNTF nerve conduit, PLGA/chitosan conduit and autologous nerve grafts were performed as the control. The results were evaluated by general observation, electromyogram testing, S-100 histological immunostaining, and image analysis at 3 months after operation. The histological results demonstrated that the PLGA/chitosan-CNTF conduits and PLGA/chitosan conduits were capable of leading the damaged axons through the lesioned area. Through the comparison of the three groups, the results in PLGA/chitosan-CNTF conduits group were better than that of PLGA/chitosan conduits group, while they were similar to autologous nerve grafts group. Therefore, CNTF-coated PLGA/chitosan nerve conduits could be an alternative artificial nerve conduit for nerve regeneration.

MMPT: a thiazolidin compound inhibits the growth of lung cancer H1792 cells via Fas-mediated and caspase-dependent apoptosis pathway.

MMPT, a thiazolidin compound, was identified in our laboratory as a novel antineoplastic agent with a broad spectrum of antitumor activity against many human cancer cells. However, the related mechanism has yet not been revealed. In this study, we investigated the cellular and molecular events underlying the antitumor function of this compound in human lung adenocarcinoma H1792 cells, focusing on the early cytotoxic effect. Treatment of H1792 cancer cells with MMPT (0.1-100 microM for 24-72 h) resulted in a growth inhibition in a dose and time-dependent manner, determined by MTT assay. This effect was accompanied by apoptosis, evidenced by Nucleosome ELISA, H33258 stained assay, and Sub-G1 analysis. Our data showed that MMPT caused activation of caspase-3, caspase-6 and caspase-8, but not caspase-9. The finding that MMPT induced apoptosis through a membrane-mediated mechanism was supported by the up-regulated expression of Fas (CD95/APO-1), and Fas ligand. Overall, our results demonstrated that MMPT induced growth inhibition of H1792 cells through a Fas-mediated and caspase-dependent apoptosis pathway, which suggested that MMPT might be used as a Fas/FasL and caspases promoter to initiate lung cancer cell apoptosis.

Effect of compound plate composition on measurement of hERG current IC(50) using PatchXpress.

Inhibition of the human ether-a-go-go-related gene (hERG) potassium channel by pharmaceutical agents can lead to acquired long QT syndrome and the generation of potentially lethal arrhythmias. Higher throughput automated patch clamp systems, such as PatchXpress, can greatly increase the speed and capacity of evaluation of pharmaceutical compounds for hERG blocking activity. A factor that may affect the IC(50) value of a compound measured in this system is the composition of the multi-well compound plate. Hydrophobic compounds may adsorb to the surfaces of multi-well plates resulting in a reduction in the effective concentration of the compound delivered to the cell and altered IC(50) values. In the present study, we investigated the effects of four different compound plates--glass vials, non-binding polystyrene, hydrophilic polystyrene, and polystyrene--on determination of IC(50)s for four compounds--sotalol, dofetilide, cisapride, and bepridil--which ranged in hydrophobicity. In addition, we investigated the effects of incubation time in the compound plate on determination of IC(50)s. hERG currents were measured using the PatchXpress 7000A Automated Parallel Patch Clamp System (Molecular Devices Corporation; Sunnyvale, CA) and hERG channels stably expressed in HEK293 cells. The results suggest that more hydrophobic compounds may adsorb to non-binding polystyrene, hydrophilic, and polystyrene compound plates versus glass plates, especially with increasing time on the plates, resulting in altered IC(50) values.

Characteristics of coronary arteriography and traditional Chinese medicine syndrome of 1,069 patients with coronary artery disease / 中西医结合学报

OBJECTIVE: To study the characteristics of coronary arteriography and traditional Chinese medicine syndrome of 1,069 patients with coronary artery disease (CAD). METHODS: One thousand and sixty-nine patients with CAD were investigated by epidemiological method. The patients were divided into young patients (n=82, aged 45 years or younger) and middle-aged and old patients (n=987, older than 45 years). The characteristics of the two groups were analyzed, including clinical data, coronary arteriography and traditional Chinese medicine syndrome. RESULTS: Compared with middle-aged and old patients, proportion of male, triglyceride, total cholesterol, smoking patients, acute myocardial infarction and family history of CAD in young patients were significantly higher (P<0.05). Patients accompanying with hypertension and diabetes in middle-aged and old patients were more than those in young patients (P<0.05). Occurrence rates of morbidity of left circumflex coronary artery, left main coronary artery and multi-branch were higher in middle-aged and old patients (P<0.05), however, the occurrence rates of morbidity of single and double-branch were higher in young patients (P<0.05). The occurrence rates of syndromes of qi stagnation and phlegm turbidity in young patients were higher than those in middle-aged and old patients (P<0.05). But the proportions of cold coagulation, yin deficiency, yang deficiency and kidney deficiency in middle-aged and old patients were obviously higher (P<0.05). CONCLUSION: The traditional Chinese medicine syndrome and pathological changes of CAD in young patients are different from those in old patients.

Evaluation of the rubidium efflux assay for preclinical identification of HERG blockade.

Inhibition of the delayed-rectifier potassium channel current, human ether-a-go-go (hERG), by pharmaceutical agents can lead to acquired long QT syndrome and the generation of potentially lethal arrhythmias and sudden death. There remains an unmet need for higher-throughput assays to screen compounds in preclinical development for the potential to block hERG and cause QT prolongation. We evaluated the rubidium efflux assay for its ability to determine block of the hERG potassium channel. hERG-transfected human embryonic kidney-293 cells were cultured on 96-well assay plates and loaded with rubidium ion by incubating in media in which potassium was replaced by 5.4 mM Rb+. Cells were exposed to test compounds and then depolarized with a K+ channel opening buffer containing 50 mM K+. The supernatant was removed, and cells were lysed using 0.1% Triton X-100. Concentration-response curves were generated for test agents by determining the Rb+ efflux using a flame atomic absorption spectrometer. Multiple trials with cisapride yielded 50% inhibitory concentration values between 308.1 +/- 11 nM to 456.3 +/- 24 nM for inhibition of Rb+ efflux and a Z factor of 0.80 +/- 0.07 (n = 5 plates, 12 wells per plate). The values for inhibition of the hERG channel exhibited a rightward shift in potency as compared to those measured using electrophysiological techniques. In addition, we evaluated 19 blinded compounds at 10 microM in the Rb+ efflux assay, and compared results to those using patch clamp electrophysiology and the dofetilide displacement binding assay. The dofetilide displacement binding assay yielded a good correlation with electrophysiological measurements of hERG block. The rubidium efflux assay lacked sensitivity to consistently identify significant channel blockade. In conclusion, the rubidium efflux assay provides a higher-throughput means to identify potent hERG channel blocking agents, but lacks the sensitivity required to accurately determine the potency of blockade.

[Study on the fluorescence of poly (amidoamine) dendrimers decorated with coumarin-3-methyl acyl chloride on the periphery].

The polyamidoamine dendrimers, PAMAM-CMAC, was synthesized by decorating PAMAM dendrimer with coumarin-3-methyl acyl chlorine on the periphery. The structures were characterized by FTIR and H-NMR spectra. The fluorescence analysis indicated the PAMAM-CMAC exhibits strong fluorescence emission. The fluorescence intensity of PAMAM-CMAC is much higher than that of PAMAM dendrimer. The fluorescence intensity of PAMAM-CMAC was affected by pH, concentration and solvent. At a considerably big pH value range, the fluorescence emission of PAMAM-CMAC is comparatively stable. Meanwhile, the fluorescence emission of PAMAM-CMAC shifts to longer wavelength with the increase in solvent polarity.

A slowly formed transient conformer of Abeta(1-40) is toxic to inward channels of dissociated hippocampal and cortical neurons of rats.

The mechanism by which amyloid peptide (Abeta(1-40)) produces effects on neurotransmission is currently unresolved. In initial experiments, using the patch-clamp technique, we found that 11.5 microM of preaggregated Abeta(1-40) altered the hippocampal neuron resting membrane potential and inhibited action potential firing. To identify the toxic species, the effects of Abeta(1-40) on sodium (I(Na)), calcium (I(Ca)), and potassium (I(K)) currents in hippocampal neurons were examined as a function of peptide aggregation state in a specially designed miniature recording chamber. Aggregation reactions were induced by constant shaking, starting with 50 microM monomeric peptide. At 10- to 30-min intervals, the ionic currents were examined on a single neuron suspended in control saline and then in a 100-microl sample of the aggregating peptide. We found that samples of the peptide taken 60-120 min into the aggregation process contained species that exhibited maximal inhibitory effects over a broad potential range in the rank ordering of I(Na) > I(Ca). I(K) was inhibited only slightly at depolarized potentials. Inhibition of APF through blockade of these channels would inhibit normal neuronal activity and directly contribute to cognitive dysfunction. In previous studies on SH-EP cells, we showed that neither monomeric nor fibrillar peptide had significant effect on cell viability except during exposure to the 60-120 minute aggregation product when cell death was recorded. Our kinetic model demonstrated that the toxic species was a slowly formed transient conformer (activated monomer), which was the only aggregating species that passed through a maximum concentration during aggregation. This species amounted to only a small fraction of the total amount of aggregating peptide. We conclude that, for both the native neurons in the present study as well as SH-EP1 cells, the activated monomeric conformer of the peptide is the toxic species.

Dendrotoxin-sensitive K(+) currents contribute to accommodation in murine spiral ganglion neurons.

We have previously identified two broad electrophysiological classes of spiral ganglion neuron that differ in their rate of accommodation (Mo & Davis, 1997a). In order to understand the underlying ionic basis of these characteristic firing patterns, we used alpha-dendrotoxin (alpha-DTX) to eliminate the contribution of a class of voltage-gated K(+) channels and assessed its effects on a variety of electrophysiological properties by using the whole-cell configuration of the patch-clamp technique. Exposure to alpha-DTX caused neurons that initially displayed rapid accommodation to fire continuously during 240 ms depolarizing test pulses within a restricted voltage range. We found a non-monotonic relationship between number of action potentials fired and membrane potential in the presence of alpha-DTX that peaked at voltages between -40 to -10 mV and declined at more depolarized and hyperpolarized test potentials. The alpha-DTX-sensitive current had two components that activated in different voltage ranges. Analysis of recordings made from acutely isolated neurons gave estimated half-maximal activation voltages of -63 and 12 mV for the two components. Because alpha-DTX blocks the Kv1.1, Kv1.2 and Kv1.6 subunits, we examined the action of the Kv1.1-selective blocker dendrotoxin K (DTX-K). We found that this antagonist reproduced the effects of alpha-DTX on neuronal firing, and that the DTX-K-sensitive current also had two separate components. These data suggest that the transformation from a rapidly adapting to a slowly adapting firing pattern was mediated by the low voltage-activated component of DTX-sensitive current with a potential contribution from the high voltage-activated component at more depolarized potentials. In addition, the effects of DTX-K indicate that Kv1.1 subunits are important constituents of the underlying voltage-gated potassium channels.

Firing features and potassium channel content of murine spiral ganglion neurons vary with cochlear location.

Neurons from varied regions of the central nervous system can show widely divergent responses to electrical stimuli that are determined by cell-specific differences in ion channel composition. The well-ordered and highly characterized peripheral auditory system allows one to explore the significance of this diversity during the final stages of postnatal development. We examined the electrophysiological features of murine spiral ganglion neurons in vitro at a time when recordings could be made from the cell bodies before myelination. These cells carry information about sound stimuli from hair cell receptors in the basilar membrane and are arranged tonotopically. Spiral ganglion neuron responses to depolarizing current injection were assessed with whole-cell current clamp recordings from cells that were isolated separately from the apical and basal thirds of the mouse cochlea. These cells displayed systematic variation in their firing. Apex neurons (low frequency coding) showed longer latency, slowly adapting responses, whereas base neurons (high frequency coding) showed short latency, rapidly adapting responses to the same stimuli. This physiological diversity was mirrored by regional differences in ion channel content assessed immunohistochemically. Apex neurons had a preponderance of Kv4.2 subunits, whereas base neurons possessed greater levels of K(Ca), Kv1.1, and Kv3.1 subunits. Taken together, these results indicate that the distribution of a set of voltage-gated potassium channels may relate specifically to a particular range of coding frequencies. These studies also suggest that intrinsic properties of spiral ganglion neurons can contribute to the characteristic responses of the peripheral auditory system. Their potential role in development and adult function is discussed.