Comparison of the application value of transvaginal ultrasound and transabdominal ultrasound in the diagnosis of ectopic pregnancy.

BACKGROUND: Ectopic pregnancy (EP) is one of the most common acute abdominal diseases in gynecology. Once the condition of EP is delayed, it may lead to massive hemorrhage, shock, and even death in a short time, seriously threatening the patient's life. Early diagnosis is the key to preventing and improving the prognosis of EP. Transabdominal ultrasound (TAS) and transvaginal ultrasound (TVS) are the main diagnostic methods for abdominal diseases. The purpose of this study is to explore the application value and effect of TAS and TVS in the diagnosis of EP, hoping to provide more valuable references for the diagnosis of EP. AIM: To explore the application value of TAS and TVS in the diagnosis of EP and to improve the level of clinical diagnosis. METHODS: A total of 140 patients with EP admitted to our hospital from July 2018 to July 2020 were selected for this study. All patients were divided into two groups according to the examination methods. 63 patients who underwent abdominal ultrasound examination were set as the TAS group, while 77 patients who underwent TVS examination were set as the TVS group. We compared the diagnostic accuracy and misdiagnosis rates between the two types of ultrasound examinations, as well as the postoperative pathological results of the two diagnostic methods for different types of ectopic pregnancies. We also analyzed the sonograms for the presence of mixed ectopic masses, adnexal masses, ectopic gestational sacs, the presence or absence of visible embryo and fetal heart in the ectopic sac shadow, and the detection of fluid in the rectal fossa of the uterus, such as the adnexal area, yolk sac, and embryo, etc. In addition, the diagnosis time, days of gestational sac appearance, operation time, endometrial thickness, and blood flow resistance index were compared as well. RESULTS: After performing both types of ultrasound examinations in 140 patients with EP, we found that the diagnostic accuracy of TVS was significantly higher than that of TAS, and the misdiagnosis rate was significantly lower than that of TAS. The differences were statistically significant (P < 0.05). In addition, the detection rate of TVS was better than that of TAS for the presence of mixed masses, adnexal masses, ectopic gestational sacs, the presence or absence of visible embryo and fetal heart in the shadow of the ectopic sac, and sonograms such as the adnexal area, yolk sac, and embryo, etc. The coincidence rate of its postoperative pathological examination results was significantly higher than those of TAS. The diagnosis time and the days of gestational sac appearance by TVS were significantly shorter than that by TAS, and the operation time was earlier than that by TAS. What's more, the detection rates of the endometrial thickness £ 1.5 mm and blood flow resistance £ 0.5 were significantly higher in TVS diagnosis of EP than in TAS. All differences were statistically significant (P < 0.05). CONCLUSION: Compared with TAS, TVS has the advantages of high detection accuracy and good sonogram performance.

[Distribution Characteristics of Heavy Metals in Farmland Soils Around Mining Areas and Pollution Assessment].

In order to explore the spatial distribution and ecological risk of heavy metals in farmland soil around Tongguan Mining area, surface soil samples from Tongguan Mining area were collected in September 2020, and the contents and distribution characteristics of eight heavy metals (Pb, Cu, Cd, Hg, Cr, Ni, Zn, and As) in the samples were analyzed. The Nemerow comprehensive pollution index and potential ecological risk index were used to evaluate soil pollution. The results showed that the contents of the eight types of heavy metal elements in this area exceeded the standard, and the exceeding rates were 97.91%, 84.79%, 100%, 95.41%, 96.87%, 98.54%, 91.45%, and 28.95%, respectively. The variation coefficients of the eight heavy metals were ranked as Hg>Pb>Cu>Cd>Zn>As>Ni>Cr. The variation coefficients of Hg, Pb, Cu, Cd, and Zn were all greater than 1. Correlation analysis showed that these five heavy metals were obviously correlated. In terms of spatial distribution, Pb, Cd, Cu, Hg, Zn, and As were distributed in patches, whereas Cr and Ni were distributed in flakes. The high values of Hg, Cd, Pb, Cu, and Zn were mainly distributed in the southern and central part of the study area. The comprehensive pollution of Nemerow showed that the severe pollution rate reached 87.91%, and the moderate pollution rate and the mild pollution rate were 9.58% and 2.5%, respectively; thus, the overall pollution was severe. The potential ecological risk index showed that Hg, Cd, Pb, and Cu were the main risk elements. The total potential ecological risk index showed that the proportion of samples with strong pollution was 97.08%, and the proportion of extremely strongly, very strongly, and strongly polluted samples were 55.63%, 27.08%, and 14.37%, respectively, indicating that the overall potential ecological risk in the study area was very strong. Combining the two pollution assessment methods, it can be seen that the heavy metal pollution around Tongguan mining area, primarily by Hg, Cd, and Pb, was serious. These results can provide data support for regional pollution control, soil remediation, and ecological protection. It is suggested that the state of soil heavy metal pollution and its transformation in various media should be monitored continuously in the future.

[Genotype, environment and their interactions of functional components in Rheum palmatum].

Eight kinds of provenance of Rheum palmatum collected from 4 provinces Sichuan, Ningxia, Gansu, Shannxi as test materials, which were transplanted under 3 different environments by using complete randomized block design with three replicates. The contents of the chemical components was determined by HPLC. This study aimed at analyzing the effect of genotype, environment and their interactions on the 4 kinds of functional components (phenolic acids, bianthrone, free anthraquinones and combined anthraquinones) in 14 kinds of active components of R. palmatum, in order to provide a theoretical basis for the selection of cultivated R. palmatum in high quality producing area and excellent provenance. The functional components of R. palmatum were influenced by genotype and environment. The content of phenolic acids was mainly influenced by environment, and the other three kinds of functional components were affected by environment and their interactions. The proportion of environment was larger. The cultivation quality of R. palmatum should give priority to environment, then choose a provenance. Sichuan may be beneficial in accumulation of free anthraquinones in R. palmatum, Gansu may facilitate the binding of combined anthraquinone, phenolic acids and bianthrone content. Preliminary inference based on the content and proportion of efficacy components, P2 could be potential special medicinal germplasm that have function of heat-clearing and detoxifying drugs. P6 could be potential special medicinal germplasm that activate blood circulation to dissipate blood stasis. P7 and P1 could all be potential specialmedicinal germplasms that exist diarrhea attack characters. The results of this study have important guiding significance for the production of rhubarb precision medicinal materials.

[Genotype, environment and their interactions of functional components in Rheum tanguticum].

Six kinds of provenance of Rheum tanguticum collected from Qinghai province as the test materials, which were transplanted under 3 different environments by using complete randomized block design with three replicates. The contents of the chemical components was determined by HPLC. This study aimed at analyzing the effect of genotype, environment and their interactions on the 4 kinds of functional components (phenolic acids, bianthrone, free anthraquinones and combined anthraquinones) in 14 kinds of active components of Rh. tanguticum, in order to provide a theoretical basis for the selection of cultivated Rh. tanguticum in high quality producing area and excellent provenance. The provenance trial showed that the genotype and environment influence on the effect of all kinds of functional components in Rh. tanguticum were significant (P<0.05). The content of phenolic acids was mainly influenced by environment, and the other three kinds of functional components were affected by environment and their interactions. The proportion of environment was larger. The cultivation quality of Rh. tanguticum should give priority to environment, then choose a provenance. Sichuan may be beneficial in accumulation of combined anthraquinones in Rh. tanguticum, Gansu may facilitate the binding of free anthraquinone, phenolic acids and bianthrone content. Preliminary inference based on the content and proportion of efficacy components, T4 could be potential special medicinal germplasm that have function of heat-clearing and detoxifying drugs and activate blood circulation to dissipate blood stasis; T3 and T6 could all be potential specialmedicinal germplasms that exist diarrhea attack characters. The results of this study have certain guiding significance for the production of rhubarb precision medicinal materials.

Distribution patterns of the contents of five biologically activate ingredients in the root of Scutellaria baicalensis.

As an important herbaceous plant, Scutellaria baicalensis Georgi (Chinese skullcap) is geographically widespread and commonly used throughout the world. In the Chinese medicine market, S. baicalensis has been divided into two primary types, "Ku Qin" (WXR) and "Tiao Qin" (TST). Moreover, TST is also divided into different grades according to the diameter of roots. To explore the distribution patterns of the contents of five biologically activate ingredients (FBAI), we used six-year-old cultivated S. baicalensis and analyzed its growth characteristics as well as the quality difference among different types and diameters in roots. Throughout the entire root, we discovered that contents of the FBAI all initially increased and subsequently decreased from the top to the bottom of the roots. The baicalin content of WXR was less than that of TST. On the contrary, the contents of baicalein, wogonin, and oroxylin A in WXR were up to about two times higher than that in TST. We also found that the 0 to 40 cm part of the S. baicalensis root possessed about 87% of the root biomass and about 92% of the contents of the active ingredients.

Clinical and radiographic observations from four patients with primary hepatic lymphoma.

The aim of the present study was to delineate the radiographic and clinical features of primary hepatic lymphoma (PHL). Four histopathologically confirmed cases of PHL were analyzed with respect to the radiological, clinical and pathological characteristics. The main clinical manifestations included upper right quadrant pain and lymphoma-associated B symptoms, such as fever, night sweating and weight loss. All the patients had elevated serum levels of lactate dehydrogenase. Furthermore, all the patients underwent plain and enhanced computed tomography examinations, which identified low-density lesions without marked enhancement. Solitary masses were observed in two cases, while multiple focal lesions were noted in one case and diffuse multi-speckled nodules were observed in one case. Two patients underwent abdominal magnetic resonance imaging, which revealed lesions that were hyperintense on T1-weighted imaging (WI) scans and hypointense on T2WI scans, and exhibited slight to moderate enhancement with a dynamic contrast-enhanced protocol. In one case, vessels were visible within the lesion. Therefore, the present study concluded that PHL is a rare condition that exhibits non-specific clinical and radiological features. A combination of imaging results and clinical manifestations can be used to facilitate a diagnosis of PHL.

Clinical utility of dual-energy CT for gout diagnosis.

OBJECTIVE: The present study was to evaluate the clinical value of dual-energy computed tomography (DECT) for detecting monosodium urate crystals in patients with gouty arthritis. METHODS: Two hundred and two patients, who experienced arthrocele and (or) joint pain, were enrolled into our study. DECT scans of upper or lower extremity were performed. One hundred and sixty one patients who conformed to the American College of Rheumatology classification standard were defined as the gout group. The rest (41) of the patients were regarded as the without-gout group. DE (80kV/140kV) datasets were reconstructed via DE gout software. Images were reviewed independently by two senior radiologists. RESULTS: In the gout group, DECT scans revealed a total of 379 areas of urate deposition in 121 patients. In the without-gout group, 3 areas of green urate deposition were detected. The sensitivity and specificity were 75.2% and 92.7%, respectively; when we increased the ratio to 1.32 and decreased the range to 3, the number of patients with green urate deposition increased, and the areas of urate deposition were more extensive. The sensitivity and specificity were 91.9% and 85.4%. DECT images could illustrate the palpable reduction in the tissue urate deposits compared to baseline images before and after treatment. CONCLUSIONS: DECT has comparable sensitivity and specificity for the detection of gouty arthritis in a clinical setting, and DECT can monitor the clinical treatment. However, DECT results should be interpreted carefully because there could be some false-negative or false-positive findings.

Primary hepatic peripheral T-cell lymphoma: A case report.

Primary hepatic peripheral T-cell lymphoma (PHL) is extremely rare. A case of primary hepatic peripheral T-cell lymphoma of a 59-year-old male is presented in the current study. PHL lesions are diagnosed by the existence of a hepatic mass, in the absence of lymphadenopathy, splenomegaly or bone marrow involvement associated with normal tumor markers. Treatment options are surgical resection and subsequent chemotherapy. Histopathological examination by immunohistochemical staining of the tissue biopsies at laparotomy confirmed a diagnosis of PHL.

Primary retroperitoneal extraskeletal mesenchymal chondrosarcoma involving the vena cava: A case report.

The current study presents a case of extraskeletal mesenchymal chondrosarcoma (ESMC) involving the vena cava that originally occurred in the retroperitoneum of a 61-year-old female. Following excision of the masses, pathological examination confirmed a diagnosis of primary ESMC. Mesenchymal chondrosarcomas are extremely rare in comparison to conventional chondrosarcomas and even more so when arising in an extraskeletal location. In the current report, the major characteristics of ESMC are discussed and a review of the current knowledge regarding this rare disease entity is presented.

Relationship between computed tomography manifestations of thymic epithelial tumors and the WHO pathological classification.

OBJECTIVE: To explore the relationship between computed tomography (CT) manifestations of thymoma and its WHO pathological classification. METHODS: One hundred and five histopathologically confirmed cases were collected for their pathological and CT characteristics and results were statistically compared between different pathological types of thymoma. RESULTS: Tumor size, shape, necrosis or cystic change, capsule integrity, invasion to the adjacent tissue, lymphadenopathy, and the presence of pleural effusion were significantly different between different pathological types of thymomas (P<0.05). Type B2, B3 tumors and thymic carcinomas were greater in size than other types. More than 50% of type B3 tumors and thymic carcinomas had a tumor size greater than 10 cm. The shape of types A, AB, and B1 tumors were mostly round or oval, whereas 75% of type B3 tumors and 85% of thymic carcinomas were irregular in shape. Necrosis or cystic change occurred in 67% of type B3 thymomas and 57% of thymic carcinomas, respectively. The respective figures for capsule destruction were 83% and 100%. Increases in the degree of malignancy were associated with increases in the incidence of surrounding tissue invasion: 33%, 75%, and 81% in type B2, type B3, and thymic carcinomas, respectively. Pleural effusion occurred in 48% of thymic carcinomas, while calcification was observed mostly in type B thymomas. CONCLUSIONS: Different pathological types of thymic epithelial tumors have different CT manifestations. Distinctive CT features of thymomas may reflect their pathological types.

Metabotropic glutamate receptor 5 regulates excitability and Kv4.2-containing K⁺ channels primarily in excitatory neurons of the spinal dorsal horn.

Metabotropic glutamate (mGlu) receptors play important roles in the modulation of nociception. Previous studies demonstrated that mGlu5 modulates nociceptive plasticity via activation of ERK signaling. We have reported recently that the Kv4.2 K(+) channel subunit underlies A-type currents in spinal cord dorsal horn neurons and that this channel is modulated by mGlu5-ERK signaling. In the present study, we tested the hypothesis that modulation of Kv4.2 by mGlu5 occurs in excitatory spinal dorsal horn neurons. With the use of a transgenic mouse strain expressing enhanced green fluorescent protein (GFP) under control of the promoter for the γ-amino butyric acid (GABA)-synthesizing enzyme, glutamic acid decarboxylase 67 (GAD67), we found that these GABAergic neurons express less Kv4.2-mediated A-type current than non-GAD67-GFP neurons. Furthermore, the mGlu1/5 agonist, (R,S)-3,5-dihydroxyphenylglycine, had no modulatory effects on A-type currents or neuronal excitability in this subgroup of GABAergic neurons but robustly modulated A-type currents and neuronal excitability in non-GFP-expressing neurons. Immunofluorescence studies revealed that Kv4.2 was highly colocalized with markers of excitatory neurons, such as vesicular glutamate transporter 1/2, PKCγ, and neurokinin 1, in cultured dorsal horn neurons. These results indicate that mGlu5-Kv4.2 signaling is associated with excitatory dorsal horn neurons and suggest that the pronociceptive effects of mGlu5 activation in the spinal cord likely involve enhanced excitability of excitatory neurons.

Metabotropic glutamate receptor 5 modulates nociceptive plasticity via extracellular signal-regulated kinase-Kv4.2 signaling in spinal cord dorsal horn neurons.

Metabotropic glutamate receptors (mGluRs) play important roles in the modulation of nociception. The group I mGluRs (mGlu1 and mGlu5) modulate nociceptive plasticity via activation of extracellular signal-regulated kinase (ERK) signaling. We reported recently that the K+ channel Kv4.2 subunit underlies A-type K+ currents in the spinal cord dorsal horn and is modulated by the ERK signaling pathway. Kv4.2-mediated A-type currents are important determinants of dorsal horn neuronal excitability and central sensitization that underlies hypersensitivity after tissue injury. In the present study, we demonstrate that ERK-mediated phosphorylation of Kv4.2 is downstream of mGlu5 activation in spinal cord dorsal horn neurons. Activation of group I mGluRs inhibited Kv4.2-mediated A-type K+ currents and increased neuronal excitability in dorsal horn neurons. These effects were mediated by activation of mGlu5, but not mGlu1, and were dependent on ERK activation. Analysis of Kv4.2 phosphorylation site mutants clearly identified S616 as the residue responsible for mGlu5-ERK-dependent modulation of A-type currents and excitability. Furthermore, nociceptive behavior induced by activation of spinal group I mGluRs was impaired in Kv4.2 knock-out mice, demonstrating that, in vivo, modulation of Kv4.2 is downstream of mGlu5 activation. Altogether, our results indicate that activation of mGlu5 leads to ERK-mediated phosphorylation and modulation of Kv4.2-containing potassium channels in dorsal horn neurons. This modulation may contribute to nociceptive plasticity and central sensitization associated with chronic inflammatory pain conditions.

The kv4.2 potassium channel subunit is required for pain plasticity.

A-type potassium currents are important determinants of neuronal excitability. In spinal cord dorsal horn neurons, A-type currents are modulated by extracellular signal-regulated kinases (ERKs), which mediate central sensitization during inflammatory pain. Here, we report that Kv4.2 mediates the majority of A-type current in dorsal horn neurons and is a critical site for modulation of neuronal excitability and nociceptive behaviors. Genetic elimination of Kv4.2 reduces A-type currents and increases excitability of dorsal horn neurons, resulting in enhanced sensitivity to tactile and thermal stimuli. Furthermore, ERK-mediated modulation of excitability in dorsal horn neurons and ERK-dependent forms of pain hypersensitivity are absent in Kv4.2(-/-) mice compared to wild-type littermates. Finally, mutational analysis of Kv4.2 indicates that S616 is the functionally relevant ERK phosphorylation site for modulation of Kv4.2-mediated currents in neurons. These results show that Kv4.2 is a downstream target of ERK in spinal cord and plays a crucial role in pain plasticity.

Impaired inflammatory pain and thermal hyperalgesia in mice expressing neuron-specific dominant negative mitogen activated protein kinase kinase (MEK).

BACKGROUND: Numerous studies have implicated spinal extracellular signal-regulated kinases (ERKs) as mediators of nociceptive plasticity. These studies have utilized pharmacological inhibition of MEK to demonstrate a role for ERK signaling in pain, but this approach cannot distinguish between effects of ERK in neuronal and non-neuronal cells. The present studies were undertaken to test the specific role of neuronal ERK in formalin-induced inflammatory pain. Dominant negative MEK (DN MEK) mutant mice in which MEK function is suppressed exclusively in neurons were tested in the formalin model of inflammatory pain. RESULTS: Formalin-induced second phase spontaneous pain behaviors as well as thermal hyperalgesia measured 1 - 3 hours post-formalin were significantly reduced in the DN MEK mice when compared to their wild type littermate controls. In addition, spinal ERK phosphorylation following formalin injection was significantly reduced in the DN MEK mice. This was not due to a reduction of the number of unmyelinated fibers in the periphery, since these were almost double the number observed in wild type controls. Further examination of the effects of suppression of MEK function on a downstream target of ERK phosphorylation, the A-type potassium channel, showed that the ERK-dependent modulation of the A-type currents is significantly reduced in neurons from DN MEK mice compared to littermate wild type controls. CONCLUSION: Our results demonstrate that the neuronal MEK-ERK pathway is indeed an important intracellular cascade that is associated with formalin-induced inflammatory pain and thermal hyperalgesia.

Blockade of L-type calcium channel in myocardium and calcium-induced contractions of vascular smooth muscle by CPU 86017.

AIM: To assess the blockade by CPU 86017 on the L-type calcium channels in the myocardium and on the Ca(2+)-related contractions of vascular smooth muscle. METHODS: The whole-cell patch-clamp was applied to investigate the blocking effect of CPU 86017 on the L-type calcium current in isolated guinea pig myocytes and contractions by KCl or phenylephrine (Phe) of the isolated rat tail arteries were measured. RESULTS: Suppression of the L-type current of the isolated myocytes by CPU 86017 was moderate, in time- and concentration-dependent manner and with no influence on the activation and inactivation curves. The IC(50) was 11.5 micromol/L. Suppressive effect of CPU 86017 on vaso-contractions induced by KCl 100 mmol/L, phenylephrine 1 micromol/L in KH solution (phase 1), Ca(2+) free KH solution ( phase 2), and by addition of CaCl(2) into Ca(2+)-free KH solution (phase 3) were observed. The IC(50) to suppress vaso-contractions by calcium entry via the receptor operated channel (ROC) and voltage-dependent channel (VDC) was 0.324 micromol/L and 16.3 micromol/L, respectively. The relative potency of CPU 86017 to suppress vascular tone by Ca(2+) entry through ROC and VDC is 1/187 of prazosin and 1/37 of verapamil, respectively. CONCLUSION: The blocking effects of CPU 86017 on the L-type calcium channel of myocardium and vessel are moderate and non-selective. CPU 86017 is approximately 50 times more potent in inhibiting ROC than VDC.

Mammalian retinal bipolar cells express inwardly rectifying K+ currents (IKir) with a different distribution than that of Ih.

Retinal bipolar cells comprise multiple subtypes that are well known for the diversity of their physiological properties. We investigated the properties and functional roles of the hyperpolarization-activated currents in mammalian retinal bipolar cells using whole cell patch-clamp recording techniques. We report that bipolar cells express inwardly rectifying K+ currents (IKir) in addition to the hyperpolarization-activated cationic currents (Ih) previously reported. Furthermore, these two currents are differentially expressed among different subtypes of bipolar cells. One group of cone bipolar cells in particular displayed mainly IKir. A second group of cone bipolar cells displayed both currents but with a much larger Ih. Rod bipolar cells, on the other hand, showed primarily Ih. Moreover, we showed that IKir and Ih differentially influence the voltage responses of bipolar cells: Ih facilitates and/or accelerates the membrane potential rebound, whereas IKir counteracts or prevents such rebound. The findings of the expression of IKir and the differential expression of Ih and IKir in bipolar cells may provide new insights into an understanding of the physiological properties of bipolar cells.

Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1).

Protein kinase C (PKC) modulates the function of the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). This modulation manifests as increased current when the channel is activated by capsaicin. In addition, studies have suggested that phosphorylation by PKC might directly gate the channel, because PKC-activating phorbol esters induce TRPV1 currents in the absence of applied ligands. To test whether PKC both modulates and gates the TRPV1 function by direct phosphorylation, we used direct sequencing to determine the major sites of PKC phosphorylation on TRPV1 intracellular domains. We then tested the ability of the PKC-activating phorbol 12-myristate 13-acetate (PMA) to potentiate capsaicin-induced currents and to directly gate TRPV1. We found that mutation of S800 to alanine significantly reduced the PMA-induced enhancement of capsaicin-evoked currents and the direct activation of TRPV1 by PMA. Mutation of S502 to alanine reduced PMA enhancement of capsaicin-evoked currents, but had no effect on direct activation of TRPV1 by PMA. Conversely, mutation of T704 to alanine had no effect on PMA enhancement of capsaicin-evoked currents but dramatically reduced direct activation of TRPV1 by PMA. These results, combined with pharmacological studies showing that inactive phorbol esters also weakly activate TRPV1, suggest that PKC-mediated phosphorylation modulates TRPV1 but does not directly gate the channel. Rather, currents induced by phorbol esters result from the combination of a weak direct ligand-like activation of TRPV1 and the phosphorylation-induced enhancement of the TRPV1 function. Furthermore, modulation of the TRPV1 function by PKC appears to involve distinct phosphorylation sites depending on the mechanism of channel activation.

ERK integrates PKA and PKC signaling in superficial dorsal horn neurons. I. Modulation of A-type K+ currents.

The transient outward potassium currents (also known as A-type currents or IA) are important determinants of neuronal excitability. In the brain, IA is modulated by protein kinase C (PKC), protein kinase A (PKA), and extracellular signal-related kinase (ERK), three kinases that have been shown to be critical modulators of nociception. We wanted to determine the effects of these kinases on IA in superficial dorsal horn neurons. Using whole cell recordings from cultured mouse spinal cord superficial dorsal horn neurons, we found that PKC and PKA both inhibit IA in these cells, and that PKC has a tonic inhibitory action on IA. Further, we provide evidence supporting the hypothesis that PKC and PKA do not modulate IA directly, but rather act as upstream activators of ERKs, which modulate IA. These results suggest that ERKs serve as signal integrators in modulation of IA in dorsal horn neurons and that modulation of A-type potassium currents may underlie aspects of central sensitization mediated by PKC, PKA, and ERKs.

ERK integrates PKA and PKC signaling in superficial dorsal horn neurons. II. Modulation of neuronal excitability.

Protein kinases belonging to the protein kinase A (PKA), protein kinase C (PKC), and extracellular signal-related kinase (ERK) families have been identified as key players in modulating nociception at the level of the spinal cord dorsal horn, yet little is known about the effects of these kinases on membrane properties of the dorsal horn neurons. PKA, PKC, and ERK exert inhibitory effects on transient potassium currents (A-type currents or IA) in mouse superficial dorsal horn neurons (Hu et al. 2003). Here we aimed to determine the effects of these kinases on action potential firing and membrane properties of these neurons to evaluate the impact of the modulation of IA (and other conductances) in these neurons. We found that activating PKC and PKA has dramatic effects on action potential firing, reflecting an increase in the excitability of superficial dorsal horn neurons. In addition, we found that inhibitors of both PKC and ERK signaling decrease the excitability of dorsal horn neurons, suggesting that these kinases exert a tonic excitation of these cells. Consistent with our findings that these kinases inhibit A-type currents, we found that PKA, PKC, and ERK act to shorten the first-spike latency after depolarization induced by current injection. In addition, activation of these kinases increases spike frequency and action potential amplitude of dorsal horn neurons. Interestingly, we found that the effects of PKA and PKC activators are blocked by inhibitors of ERK signaling, suggesting that PKA and PKC may exert their actions by activation of ERKs.

Differential expression of K+ currents in mammalian retinal bipolar cells.

Whole-cell voltage-clamp recordings were performed to investigate voltage-dependent K+ currents in acutely isolated retinal cone bipolar cells (CBCs) from the rat. The physiological and pharmacological properties of the currents were compared with those in rod bipolar cells (RBCs). The K+ currents were found to be much larger in CBC than in RBCs. In addition, the currents in CBCs were activated and inactivated at more negative potentials. Based on the apparent inactivation property of the currents, CBCs were found to fall into two groups of cells that differed in the inactivation kinetics of IK(V) but did not correlate to the ON- and OFF-type. The IK(V) for the group of CBCs showing faster inactivation, as well as for all RBCs, contained two components with decay time constants around 0.1 and 1 s. The IK(V) for the group of CBCs showing slower inactivation only contained the slower component. Furthermore, three components of IK(V) were observed based on tetraethylammonium (TEA) sensitivity: high-sensitive, low-sensitive, and resistant component. The IK(V) for a portion of CBCs showing faster inactivation, as well as for all RBCs, contained all three components. The IK(V) for the remaining CBCs, including all of those CBCs showing slower inactivation, only contained the latter two components. This study reveals a differential expression of K+ currents in rat retinal bipolar cells, suggesting that K+ channels may play an important role in bipolar cell processing in mammalian retinas.