Mechanism of the therapeutic effect of Tetrandrine on striatum injury caused by microwave radiation / 中华放射医学与防护杂志

Objective:To study the therapeutic effect Tetrandrine (TET) on striatal injury caused by microwave radiation and underlying mechanism.Methods:C57BL/6N mice were randomly divided into blank control group (C), radiation control group (R), TET group (TET) and TET combined with radiation group (TET+ R). The mice of radiation group were exposed to 2.856 GHz 8 mW/cm2 microwave on whole-body for 15 min. TET (60 mg/kg) was injected intraperitoneally once a day for 3 consecutive days. The TET structure was verified by ultraviolet spectrophotometry. The open field experiment was used to detect the change of anxiety in mice. Histopathological and ultrastructural changes of the striatum were observed by light microscopy and transmission electron microscopy (TMT). Quantitative real-time PCR (qPCR) was used to detect gene expression changes of voltage-gated calcium channel (VGCC) subtype in the striatum.Results:The open field experiments showed that the time and distance of mice to explore the central region after microwave radiation were significantly lower than that before radiation ( t=4.60, 5.18, P<0.01), and the TET administration significantly improved these changes ( F=1.43, 4.37, P < 0.05). 7 d after microwave radiation, some neuronal nuclei in the striatum of mice contracted and could be stained deeply, which was more obvious in the globus pallidus area. The partial neuronal apoptosis, swelling and cavitation of glial cell mitochondria, blurring of synaptic gaps, and widening of perivascular gaps in the striatum were observed by TMT. The above lesions were significantly rescued after TET administration. But both microwave radiation and TET administration had no significant effect on the gene expressions of striatal VGCC ( P > 0.05). Conclusions:TET has a therapeutic effect on anxiety-like behavior and structural damage of striatum caused by microwave radiation, which is independent of the expression of striatal VGCC genes.

Research progress of voltage-gated Calcium channel gene mutations associated with epilepsy in children / 中华实用儿科临床杂志

Abnormal expression and dysfunction of voltage-gated Calcium channels (VGCCs) can give rise to a variety of neurological disorders in children, including epilepsy, migraine and ataxia.In the past, only CACNA1A, CACNA1H, CACNA2D2 and CACNB4 were considered associated with epilepsy in children.In recent years, an increasing number of VGCCs gene associated with epilepsy in children have been found, especially developmental and epileptic encephalopathy genes.This study aims to review the research progress of VGCCs gene mutations associated with epilepsy in children.

The insulinotropic effects and its relevant mechanism of telmisartan in rats / 中国药理学通报

Aim To investigate the insulinotropic effect of telmisartan anrl the underlying electrophysiological mechanism.Methods Islets and cells were isolated from Wistar rats.Islets were incubated with drugs un¬der different conditions, then supernatant liquid was collected for insulin secretion.Intracellular Ca" + ( Ca'+ j) levels of (3-cells were measured by calcium imaging technology.Patch-clamp technology was ap¬plied to detect effects on voltage-gated potassium chan¬nel ( Kv ) , and voltage-gated calcium channel ( VGCC ).Results Not affecting insulin secretion un¬der low glucose condition, telmisartan dose-dependent- ly stimulated insulin secretion under high glucose con¬ dition, and stimulation was enhanced with increasing glucose concentration.Acute increases of Ca' + concentration were elicited by telmisartan under high glucose condition.Telmisartan decreased current den¬sity of Kv channel, and increased VGCC current densi¬ty.Conclusions Telmisartan enhanced Ca~+ ; lev¬els of p-cells through its action on Kv channel and VGCC, thereby amplifying glucose-stimulated insulin secretion.

Study on effect of voltage-gated calcium channel protein in meridian tissue cells exciting conduction / 中国针灸

<p><b>OBJECTIVE</b>To explore the material basis of conduction along meridian.</p><p><b>METHODS</b>Sixty SD rats(30 males,30 females) were randomly assigned into a normal group,an acupuncture group,a verapamil blocking group and a 0.9%NaCl blocking group(control group),15 rats in each one. Fluo 3-AM(calcium fluorescence probe) was injected at the observation part in femoral stomach meridian of foot-(meridian part) and the approaching femoral meridian part(non-meridian part) in the normal group and the acupuncture group,and then incubation was applied. In the verapamil blocking group,verapamil was injected at local meridian part and non-meridian part,and in the control group 0.9%NaCl was injected. Then Fluo 3-AM was injected at the meridian part and non-meridian part in the two groups,and incubation was implemented. Caimaging changes in cells were recorded for more than 20 min after injection of every part in each group respectively. After the above operations in the last three groups,acupuncture was used at "Zusanli"(ST 36) immediately,with electroacupuncture for one min,then Caimaging changes in cells at the meridian and non-meridian parts were recorded for more than 20 min.</p><p><b>RESULTS</b>In the normal group, Cafluorescence intensity at the meridian part was higher than that at the non-meridian part. In the acupuncture group,after acupuncture Cafluorescence intensity at the meridian part was obviously higher than before,but the change before and after acupuncture was not apparent at the non-meridian part. After verapamil blocking local calcium channel and acupuncture,the Cafluorescence of the meridian part did not strengthen,and the change of that before and after acupuncture at the non-meridian part was not obvious. In the control group,after injecting 0.9%NaCl at local part,Cafluorescence intensities of the meridian and non-meridian parts showed no obvious change,so was that before and after acupuncture.</p><p><b>CONCLUSIONS</b>The voltage-gated calcium channel at the meridian part is highly correlated with its tissue cells exciting conduction.</p>

Non-paraneoplastic Lambert-Eaton myasthenic syndrome: a brief review of 10 cases / Síndrome miastênica de Lambert-Eaton não paraneoplásica: uma breve revisão de dez casos

Lambert-Eaton myasthenic syndrome (LEMS) is an immune-mediated disorder of the presynaptic neuromuscular transmission, which more frequently occurs as the remote effect of a neoplasm, in the paraneoplastic form (P-LEMS), or in a non-paraneoplastic form (NP-LEMS); but few studies describe the clinical features of NP-LEMS. We analyzed the clinical manifestations, laboratory findings, electrophysiological studies, and treatment responses in ten Brazilian patients suffering from NP-LEMS. The mean age was 41.5 years. More often neurological findings were hyporeflexia or areflexia with a post-exercise improvement. Treatment response occurred with pyridostigmine, guanidine, prednisone, azathioprine, and cyclosporine; but not response was observed after intravenous immunoglobulin and plasma exchange. Age at onset, clinical manifestations, and electrophysiological abnormalities can help more in the diagnosis than serum antibodies; the symptomatic treatment with pyridostigmine was effective; and the immunosuppressive treatment with prednisone, azathioprine, or cyclosporine was more beneficial than plasma exchange or intravenous immunoglobulin treatment.

A síndrome miastênica de Lambert-Eaton (LEMS) é uma desordem imunomediada da transmissão neuromuscular pré-sinaptica, que mais frequentemente ocorre como efeito à distância de uma neoplasia, na forma paraneoplásica (P-LEMS), ou na forma não paraneoplásica (NP-LEMS); porém poucos estudos têm descrito as características da NP-LEMS. Nós analisamos as manifestações clínicas, laboratoriais, eletrofisiológicas, e resposta ao tratamento em dez pacientes brasileiros com NP-LEMS. A idade média foi de 41,5 anos. A manifestação neurológica mais freqüente foi hiporeflexia ou arreflexia com melhora após o exercício. A resposta ao tratamento ocorreu com piridostigmina, guanidina, prednisona, azatioprina, e ciclosporina; mas não com imunoglobulina intravenosa e plasmaférese. A idade de início, manifestações clínicas e eletrofisiológicas ajudaram mais no diagnóstico do que os anticorpos séricos; o tratamento sintomático com piridostigmina foi efetivo; e o tratamento imunossupressor com prednisona, azatioprina, ou ciclosporina beneficiou mais do que a plasmaférese ou a imunoglobulina intravenosa.

Calcium Ions are Involved in Modulation of Melittin-induced Nociception in Rat: I. Effect of Voltage-gated Calcium Channel Antagonist

Melittin-induced nociceptive responses are mediated by selective activation of capsaicin-sensitive primary afferent fibers and are modulated by excitatory amino acid receptor, cyclooxygenase, protein kinase C and serotonin receptor. The present study was undertaken to investigate the peripheral and spinal actions of voltage-gated calcium channel antagonists on melittin-induced nociceptive responses. Changes in mechanical threshold and number of flinchings were measured after intraplantar (i.pl.) injection of melittin (30microg/paw) into mid-plantar area of hindpaw. L-type calcium channel antagonists, verapamil [intrathecal (i.t.), 6 or 12microg; i.pl.,100 & 200microg; i.p., 10 or 30 mg], N-type calcium channel blocker, omega-conotoxin GVIA (i.t., 0.1 or 0.5microg; i.pl., 5microg) and P-type calcium channel antagonist, omega-agatoxin IVA (i.t., 0.5microg; i.pl., 5microg) were administered 20 min before or 60 min after i.pl. injection of melittin. Intraplantar pre-treatment and i.t. pre- or post-treatment of verapamil and omega-conotoxin GVIA dose-dependently attenuated the reduction of mechanical threshold, and melittin-induced flinchings were inhibited by i.pl. or i.t. pre-treatment of both antagonists. P-type calcium channel blocker, omega-agatoxin IVA, had significant inhibitory action on flinching behaviors, but had a limited effect on melittin-induced decrease in mechanical threshold. These experimental findings suggest that verapamil and omega-conotoxin GVIA can inhibit the development and maintenance of melittin-induced nociceptive responses.

Immunohistochemical Study on the Distribution of the Voltage-gated Ion Channels in Gerbil Cerebellum / 체질인류학회지

There is growing evidence that alterations in Ca2+ homeostasis may play a role in processes of brain aging and neurodegeneration. However, few have focused on voltage-gated Ca2+ channel (VGCC) subunits, much less on expression of other voltage-gated ion channels, i.e. voltage-gated K+ (Kv) and Na+ (Nav) channels. In the present study, we have investigated the spatial patterning of VGCCs, Kv1 and Nav channels by immunohistochemistry. This study have shown clearly that the VGCCs, Kv1 and Nav channels have differential distribution in the cerebellum of gerbil, which is used as an ischemia and epilepsy animal model. Immunoreactivities for Cav2.1, Cav1.2 and Cav1.3 were observed in the cell bodies and dendritic branches of Purkinje cells. In particular, Cav1.3 immunoreactivity was most prominent in the cell bodies and dendritic arborizations. A distinct band of punctate immunoreactivity for the Cav2.1, Cav2.2, Cav1.2 and Cav1.3 were observed in cerebellar nuclei. Strong immunoreactivities for Kv1.3, Kv1.4, Kv1.5 and Kv1.6 were observed in the Purkinje cell bodies, whereas Kv1.2 immunoreactivity was found in the basket cell axon plexus and terminal regions around the Purkinje cells. In the cerebellar nuclei, Kv1.2, Kv1.4 and Kv1.6 proteins were clearly detected in the soma of cerebellar output neurons. The most intense staining for Nav1.1 was observed in the granular layer, whereas strong immunoreactivity for Nav1.2 were seen in the Purkinje cell bodies, and extended into their dendrites. The overall results have demonstrated the expression patterns of VGCCs, Kv1 and Nav channels in gerbil cerebellum. Further studies are needed to define changes in other Ca2+ channel types to determine whether any channel changes represent selective loss of specific receptors or of cell loss, and to determine whether changes in Kv and Nav channels are linked to Ca2+ channel changes.

Relationship among different types and subunits of calcium channels and antihypertensive drugs / 中国药理学通报

This paper elucidates the relationship among different types and subunits of voltage-gated calcium channels and antihypertensive drugs.①L-type calcium channels lack of functional expression in renal efferent arterioles,but it has been found recently that T-type calcium channels have had roles in the regulation of renal efferent arteriolar tone.Third generation dihydropyridine,L-type calcium channel antagonists including manidipine,nilvadipine,benzindamine and efonidipine,can dilate both afferent and efferent renal arterioles,then improve glomerular hypertension and provide renoprotection,because the inhibition of both L and T type calcium channels.② In hypertensive rats,an increased expression of L-type calcium channel ?1c subunits has been shown.and this increased expression of calcium channel ?1c subunit associated with the increase of Ca2+ influx and elevated arterial tone can be observed.These findings provide a rational basis for designing antihypertension therapy by normalizing Ca2+ channel ?1c subunit expression.