Muerte súbita inesperada en epilepsia. Revisión sobre la implicación del tallo encefálico / Sudden unexpected death in epilepsy. Review about the brainstem involvement

RESUMEN La muerte súbita inesperada en epilepsia, se define como la muerte repentina -presenciada o no- de personas con epilepsia, no traumática ni por ahogamiento, con o sin evidencias de crisis, y en quienes el examen postmorten no revela una causa estructural o toxicológica de muerte. El objetivo de esta revisión es describir las evidencias más recientes, publicadas en la literatura, sobre la participación crucial del tallo encefálico en la fisiopatología de la muerte súbita inesperada en epilepsia. Se realizó una búsqueda bibliográfica en la base de datos computarizada PubMed. Los estudios en modelos animales han demostrado que los mecanismos de la muerte súbita inesperada en epilepsia involucran un primer evento mediado por una crisis, seguido por la despolarización cortical, que se propaga al tallo encefálico y que resulta en una disfunción autonómica causante de apnea central, edema pulmonar o arritmia cardiaca. Los estudios en humanos se han apoyado en las imágenes de resonancia magnética para evaluar el papel de diferentes áreas del tallo encefálico en la muerte súbita inesperada en epilepsia. Las evidencias acumuladas por la literatura, tanto en estudios con animales como humanos, evidencian el papel fundamental desempeñado por las estructuras del tallo encefálico en la fisiopatología de la muerte súbita inesperada en epilepsia.

ABSTRACT Sudden unexpected death in epilepsy is defined as the sudden death-whether witnessed or not-of people with epilepsy, not traumatic or due to drowning, with or without evidence of seizures, and in whom postmortem examination does not reveal a structural or toxicological cause of death. The aim of this review is to describe the most recent evidence published in the literature, on the crucial involvement of the brain stem in the pathophysiology of sudden unexpected death in epilepsy. A bibliographic search was conducted in PubMed computerized database. Studies in animal models have shown that the mechanisms of sudden unexpected death in epilepsy involve a first seizure-mediated event, followed by cortical depolarization, which spreads to the brainstem and results in autonomic dysfunction causing central apnea, pulmonary edema or cardiac arrhythmia. Studies in humans have relied on magnetic resonance imaging to assess the role of the brainstem in sudden unexpected death in epilepsy. The evidence accumulated in the literature, both in animal and in human studies, shows the role played by brainstem structures in the pathophysiology of sudden unexpected death in epilepsy.

Canales de calcio como blanco de interés farmacológico / Calcium channels as a pharmacological target

Resumen Los canales de calcio son proteínas de membrana que constituyen la vía más importante para el ingreso del ion calcio (Ca2+) a la célula. Al abrirse, permiten el ingreso selectivo del ion, iniciando una variedad de procesos como contracción muscular, secreción endocrina y liberación de neurotransmisores, entre otros. Estas proteínas se agrupan en tres categorías de acuerdo con sus propiedades estructurales y funcionales: (i) Canales de Ca2+ operados por interacción receptor-ligando (ROCC), (ii) Canales activados por parámetros físicos (Transient Receptor Potencial, TRP) y (iii) Canales de Calcio dependientes de voltaje (VDCCs), siendo estos últimos los más estudiados debido a su presencia en células excitables. Dada la importancia de Ca2+ en la fisiología celular, los canales de Ca2+ constituyen un punto de acción farmacológica importante para múltiples tratamientos y, por tanto, son objeto de estudio para el desarrollo de nuevos fármacos. El objetivo de esta revisión es explicar la importancia de los canales de Ca2+ desde una proyección farmacológica, a partir de la exploración documental de artículos publicados hasta la fecha teniendo en cuenta temas relacionados con la estructura de los canales Ca2+, sus propiedades biofísicas, localización celular, funcionamiento y su interacción farmacológica.

Abstract Calcium channels are membrane proteins that constitute the most important route for the entry of the calcium ion (Ca2+) into the cell. When opened, they allow selective ion entrance, starting a variety of processes such as muscular contraction, endocrine secretion and neurotransmitters release, among others. These proteins are classified in three categories according to their structural and functional properties: (i) Receptor-operated calcium channels (ROCC), (ii) Channels activated by physical parameters (Transient Receptor Potential or TRP-channels) and (iii) Voltage-dependent calcium channels (VDCCs), the latter being the most studied due to its presence in excitable cells. Given the importance of Ca2+ in the cellular physiology, the calcium channels constitute targets for pharmacological action for multiple treatments, and therefore, they are object of study for the development of new medicaments. The objective of this review is to explain the importance of the channels of Ca2+ from a pharmacological projection, by exploring the articles published, bearing in mind topics related to the structure of the channels Ca2+, properties of their biophysics, cellular location, functioning and their pharmacological interaction.

Mechanism of berberine on the proliferation of pterygium fibroblasts / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the effect of berberine on proliferation of <i>in vitro</i> pterygium fibroblasts and its possible mechanism.<p>METHODS: Pterygium fibroblast obtained from cultured pterygium tissue after surgical excision. Pterygium fibroblasts cells apoptosis level, mitochondrial membrane potential and apoptosis-related factors mRNA and protein expression levels were detected after the induction of berberine with different final concentrations(0, 20, 40, 80μmol/L).<p>RESULTS: Berberine increased the mitochondrial depolarization level, apoptosis rate, expression level of pro-apoptotic gene Bax, Bad mRNA and protein, and decreased the expression level of Bcl-2 gene mRNA and protein <i>in vitro</i> pterygium fibroblasts cells in a dose-dependent manner. <p>CONCLUSION: Berberine may induce <i>in vitro</i> cultured pterygium cell apoptosis by increasing mitochondrial depolarization.

Effects of CC chemokine ligand 2 on pain behavior in a rat model of bone cancer pain and its underlying peripheral mechanism / 上海交通大学学报（医学版）

Objective • To investigate the effects of CC chemokine ligand 2 (CCL2) on pain behavior in a rat model of bone cancer pain (BCP) and the underlying peripheral mechanisms. Methods • BCP models were developed by inoculation of Walker256 mammary gland carcinoma cells into the tibia medullary cavities of right hind limbs SD rats. The same volume of saline was injected in sham operation (sham) group. The mechanical pain threshold was measured to judge the success of BCP model. Expression of CCL2 in L4 and L5 dorsal root ganglion (DRG) was detected by immunofluorescence staining. CCL2 (500 ng, 25 μL) was injected into plantar of the operated side to observe its effects on leg-raising and foot-licking behaviors of hind paws in BCP and sham rats. Whole-cell patch-clamp recording was used to investigate the effects of CCL2 on membrane potential of acutely dissociated DRG neurons from the two groups. Results • Fourteen days after operation, the mechanical pain threshold in the right hind paws of BCP rats was significantly lower than that in sham rats. Compared with the Sham rats, the expression of CCL2 in L4 and L5 DRG of BCP rats was significantly higher. Plantar injection of CCL2 increased paw lift time in BCP rats. The rate and amplitude of depolarization induced by CCL2 in BCP DRG neurons were significantly higher than those in sham neurons. Conclusion • CCL2 facilitates pain behavior in BCP rats, and its peripheral mechanism maybe involves CCL2-induced neuron depolarization to enhance excitability of DRG neurons. These results indicate that CCL2 plays an important role in development of BCP.

Depolarizing Effectors of Bradykinin Signaling in Nociceptor Excitation in Pain Perception

Inflammation is one of the main causes of pathologic pain. Knowledge of the molecular links between inflammatory signals and pain-mediating neuronal signals is essential for understanding the mechanisms behind pain exacerbation. Some inflammatory mediators directly modulate the excitability of pain-mediating neurons by contacting the receptor molecules expressed in those neurons. For decades, many discoveries have accumulated regarding intraneuronal signals from receptor activation through electrical depolarization for bradykinin, a major inflammatory mediator that is able to both excite and sensitize pain-mediating nociceptor neurons. Here, we focus on the final effectors of depolarization, the neuronal ion channels, whose functionalities are specifically affected by bradykinin stimulation. Particular G-protein coupled signaling cascades specialized for each specific depolarizer ion channels are summarized. Some of these ion channels not only serve as downstream effectors but also play critical roles in relaying specific pain modalities such as thermal or mechanical pain. Accordingly, specific pain phenotypes altered by bradykinin stimulation are also discussed. Some members of the effector ion channels are both activated and sensitized by bradykinin-induced neuronal signaling, while others only sensitized or inhibited, which are also introduced. The present overview of the effect of bradykinin on nociceptor neuronal excitability at the molecular level may contribute to better understanding of an important aspect of inflammatory pain and help future design of further research on the components involved and pain modulating strategies.

P wave

The electrical impulses of atrium arise from the sinus node, subsequently pass through the right and left atrium, and finally arrive at the atrioventricular node. The P wave is the summation of the electrical current generated by depolarization due to its passage through the atrial conduction pathway. It provides many clinical clues that may be useful for diagnosis of atrial, ventricular, or valvular heart diseases. This review article briefly describes the clinical implications, mechanism of genesis, and normal and pathologic features of the P wave.

Research progress in rebound depolarization of neurons / 中国病理生理杂志

[ ABSTRACT] Rebound depolarization is a special phenomenon of the neurons which generates action potential fol-lowed by a hyperpolarization stimulation.It can be recorded in many kinds of neurons and is the intrinsic membrane charac-teristic of them.Rebound depolarization plays an important role in regulating the firing pattern, rhythmic activity and sy-naptic plasticity of neurons.This review focuses on the basic characteristics, the function and mechanism of the rebound depolarization in physiological and pathological conditions, which provides reference for the clinical treatment of rebound depolarization-related diseases.

Cardiac sodium channel, its mutations and their spectrum of arrhythmia phenotypes

The mechanisms of cellular excitability and propagation of electrical signals in the cardiac muscle are very important functionally and pathologically. The heart is constituted by three types of muscle: atrial, ventricular, and specialized excitatory and conducting fibers. From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a significant aspect for the diagnosis and treatment of heart diseases. Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. There are areas in the cardiac muscle with anatomical and functional differentiation that present automatism, thus subjecting the rest of the fibers to their own rhythm. The rate of these (pacemaker) areas could be altered by modifications in ions, temperature and especially, the autonomic system. Excitability is a property of the myocardium to react when stimulated. Another electrical property is conductivity, which is characterized by a conduction and activation process, where the action potential, by the all-or-nothing law, travels throughout the heart. Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. In the gene mutation aspects that encode the rapid sodium channel (SCN5A gene), this channel is responsible for several phenotypes, such as Brugada syndrome, idiopathic ventricular fibrillation, dilated cardiomyopathy, early repolarization syndrome, familial atrial fibrillation, variant 3 of long QT syndrome, multifocal ectopic ventricular contractions originating in Purkinje arborizations, progressive cardiac conduction defect (Lenègre disease), sudden infant death syndrome, sick sinus syndrome, sudden unexplained nocturnal death syndrome, among other sodium channel alterations with clinical overlapping. Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the alpha subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment.

Os mecanismos da excitabilidade celular e de propagação dos sinais elétricos no músculo cardíaco são de grande importância funcional e patológica. O coração é composto por três tipos de músculo: atrial, ventricular e das fibras especializadas excitatórias e condutoras. Do ponto de vista fisiológico e fisiopatológico os estados conformacionais do canal de sódio constitui-se um importante aspecto para o diagnóstico e tratamento de doenças cardíacas. A descrição dos estados funcionais do canal de sódio (fechado, aberto e inativado) e sua estrutura ajudam a compreensão dos processos de regulação cardíaca. Há áreas no músculo cardíaco com diferenciação anatômica e funcional que possuem automatismo submetendo as demais fibras ao seu próprio ritmo. A frequência dessas áreas (marca-passo) pode ser alterada por modificações iônicas, pela temperatura e, especialmente, do sistema autonômico. Já a excitabilidade é a propriedade que tem o miocárdio de reagir quando estimulado. A outra propriedade elétrica é a condutibilidade, que se caracteriza por um processo de condução e ativação, no qual o potencial de ação, pela ei do tudo ou nada, percorre todo o coração. Destaca-se que o relaxamento do coração também é um processo ativo, dependente de gasto energético e de ações iônicas e enzimáticas específicas, destacando o papel dos canais de sódio no processo funcional. Nos aspectos das mutações no gene que codifica o canal rápido de sódio (gene SCN5A), este é responsável por vários fenótipos, tais como a síndrome de Brugada; a fibrilação ventricular idiopática, a miocardiopatia dilatada; a síndrome de repolarização precoce; a fibrilação atrial familiar; a síndrome do QT longo variante 3; as contrações ventriculares ectópicas multifocais originadas nas arborizações de Purkinje; o distúrbio progressivo de condução intraventricular cardíaco (doença de Lenègre); a síndrome da morte súbita do recém-nascido; a síndrome do nódulo sinusal doente; a síndrome da morte súbita noturna inesperada, entre outras alterações do canal de sódio com sobreposições clínicas, as chamadas "overpping". Por fim, parece ser apropriado considerar a "síndrome do canal de sódio" (mutações no gene da subunidade alfa do canal de sódio, gene SCN5A) como uma entidade clínica única que pode manifestar-se com um amplo espectro de fenótipos e assim, prover um melhor entendimento destas síndromes cardíacas e potencial desfecho para seu tratamento clínico.

Comparision of Partially and Totally Depolarization of Peripheral Nerve in Total Knee Arthroplasty / 中国康复理论与实践

Objective To compare the effects of peripatellar peripheral nerve partially and totally depolarized in total knee arthroplasty (TKA). Methods 66 TKA patients were divided into partially depolarized group (A, 42 knees) and totally depolarized group (B, 38 knees). The scores of knee-joint, Feller and Visual Analogue Scale were recorded. Results There was no significant difference in all the scores be-tween 2 groups before operation (P>0.05). All the scores improved after operation (P0.05). Conclusion Patellar peripheral nerve partially depolarization technique can reduce postoperative knee pain, which has the same effect with totally depolarization.

Comparision of Partially and Totally Depolarization of Peripheral Nerve in Total Knee Arthroplasty / 中国康复理论与实践

@#Objective To compare the effects of peripatellar peripheral nerve partially and totally depolarized in total knee arthroplasty (TKA). Methods 66 TKA patients were divided into partially depolarized group (A, 42 knees) and totally depolarized group (B, 38 knees). The scores of knee-joint, Feller and Visual Analogue Scale were recorded. Results There was no significant difference in all the scores between 2 groups before operation (P>0.05). All the scores improved after operation (P<0.05), however, there was still no significant difference between 2 groups (P>0.05). Conclusion Patellar peripheral nerve partially depolarization technique can reduce postoperative knee pain, which has the same effect with totally depolarization.

Uroguanylin induces electroencephalographic spikes in rats / Uroguanilina induz potenciais em espiga no eletroencefalograma de ratos

Uroguanylin (UGN) is an endogenous peptide that acts on membrane-bound guanylate cyclase receptors of intestinal and renal cells increasing cGMP production and regulating electrolyte and water epithelial transport. Recent research works demonstrate the expression of this peptide and its receptor in the central nervous system. The current work was undertaken in order to evaluate modifications of electroencephalographic spectra (EEG) in anesthetized Wistar rats, submitted to intracisternal infusion of uroguanylin (0.0125 nmoles/min or 0.04 nmoles/min). The current observations demonstrate that 0.0125 nmoles/min and 0.04 nmoles/min intracisternal infusion of UGN significantly enhances amplitude and frequency of sharp waves and evoked spikes (p = 0.03). No statistical significance was observed on absolute alpha and theta spectra amplitude. The present data suggest that UGN acts on bioelectrogenesis of cortical cells by inducing hypersynchronic firing of neurons. This effect is blocked by nedocromil, suggesting that UGN acts by increasing the activity of chloride channels.

A uroguanilina (UGN) é um peptídeo endógeno que age em receptores do tipo guanilato ciclase de membrana de células intestinais e renais aumentando a produção de GMPc e regulando o transporte epitelial de eletrólitos e água. Pesquisas recentes demonstraram a expressão deste peptídeo e de seus receptores no sistema nervosa central. O presente trabalho foi realizado com objetivo de avaliar possíveis mudanças no espectro do eletroencefalograma (EEG) de ratos Wistar anestesiados, submetidos à infusão intracisternal de uroguanilina (0.0125 nmoles/min or 0.04 nmoles/min). Os resultados apresentados no corrente trabalho demonstram que a infusão intracisternal de ambas as doses de UGN aumenta significativamente a amplitude e frequência das espículas (p = 0.03). Não foram encontradas diferenças estatísticas na amplitude absoluta dos espectros alfa ou teta. Os dados apresentados neste trabalho mostram que a UGN age na bioeletrogênese de células corticais induzindo disparo hipersincrônico de neurônios. Este efeito é bloqueado por nedocromil, sugerindo que UGN atua pelo aumento de atividade de canais de cloreto.

Correlation Analysis of Epicardial Depolarization Wave Based on Combined Unipolar and Bipolar Mapping Technique / 航天医学与医学工程

Objective To find a method for real-time measurement of epicardial electrical activity suitable for clinical application.Method Combined unipolar and bipolar mapping technique for recording epicardial electrical activity was applied to detect the propagation of depolarization wave over the epicardium.Epicardial signals from 4 pigs were sampled simultaneously during sinus rhythm or atrial fibrillation(AF).Result Active isopotential map showing the spread of excitation on epicardial surface was demonstrated and correlation analysis data were obtained.The difference in correlation coefficients between adjacent sites was evident during sinus rhythm(above 0.8) and AF(about(0.5).) Conclusion The result shows that combined unipolar and bipolar technique improves the electrode efficiency and the precision in epicardial mapping.Distribution of depolarization wave or the reentry pathway during complex arrhythmia may be revealed by correlation analysis.

Regulation of the Circadian Gene CLOCK Expression by KCl Depolarization in B35 Rat Neuroblastoma Cells / 신경정신의학

OBJECTIVES: To investigate the effects of KCl on regulation of circadian gene CLOCK expression, we observed whether induction of CLOCK is influenced by KCl depolarization in B35 rat neuroblastoma cells. METHODS: B35 rat neuroblastoma cells were grown in Dulbecco's modified Eagle's medium supplemented with 10% FBS and 1% penicillin-streptomycin in a 37 degrees C humidified incubator with 5% CO2. Inhibitors including cycloheximide and actinomycin D were pretreated 1 hour before treatment with 50mM KCl. Immunoblotting with anti-CLOCK antibody was done. RESULTS: CLCOK is induced by 50 mM KCl in B35 Rat Neuroblastoma cells, and a maximal induction in CLOCK level reached peak at 8 to 20 hours. The pretreatment of cycloheximide and actinomycin D prevented the induction of CLOCK by 50 mM KCl. CONCLUSION: We suggest that KCl depolarization may play critical roles in several aspects of the circadian gene CLOCK expression.

Analog design of magnetic resonance imaging principle / 医疗卫生装备

By using VB program and FLASH making technique,the forming principle of electrocardiogram is vividly displayed,so that the students can understand it well.

Effects of verapamil on the sustained depolarization of rat diaphragm myocyte pretreated with neostigmine or 3,4-diaminopyridine / 中国药理学与毒理学杂志

AIM　To study the effects of verapamil on end-plate potentials(EPPs) in isolated non-uniform stretched muscle preparation(INSMP) of rat diaphragms pretreated with neostigmine or 3,4-diaminopyridine(3,4-DAP). METHODS　Using conventional intracellular microelectrode recording technique. RESULTS A sustained depolarization could be induced at the end-plate area pre-incubated with 0.2－5.0 μmol·L-1 neostigmine or 1.0－4.0 mmol·L-1 3,4-DAP. In normal Tyrode solution, verapamil at a concentration of 1, 5, 10 or 20 μmol·L-1 had no significant effect on evoked endplate potentials and miniature endplate potentials. However, the sustained depolarization due to neostigmine or 3,4-DAP could be antagonized by verapamil at 5－20 μmol·L-1 and the duration of the depolarization was shortened in a concentration-dependent manner. CONCLUSIONL-type calcium ion channels can be activated by accumulated acetylcholine in the synaptic cleft and may be involved in producing sustained depolarization, while they play no role in transmitter release under normal physiological conditions.

Effect of Neurotrophins and Depolarization on Survival of Spiral Ganglion Neurons in Dissociation Cell Culture / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Several neurotrophic factors have been shown to play an essential trophic role in the development, maintenance and regulation of neuronal function. Specific neurotrophins are currently used in clinical trials for the treatment of some neurodegenerative diseases. The purposes of this experiment were twofold. Firstly, we aimed to determine the trophic effects of BDNF, NT-3, and 25 mM K+ on auditory neurons in dissociated cultures of early postnatal spiral ganglia. Secondly, we tried to collect pure neural cells after dissociating the spiral ganglions using the immunomagnetic sorting method with one of neuronal surface antigens. MATERIALS AND METHODS: Dissociated spiral ganglion cell cultures were pre-pared from cochleae of Sprague Dawley rats of 5-6 days old, and maintained in a neurobasal medium with modified N2 supplements. BDNF (50 ng/ml), NT-3 (50 ng/ml), and 25 mM K+ were added to the cultures, respectively. These cells were grown during the time course (24hr, 48hr, 72hr, 98hr) and stained with NF-200 to identify survival of spiral ganglion neurons. Immunomagnetic cell sorting for separation of spiral ganglion neurons in dissociated cells was carried out using the MiniMACS Separating System. Magnetically separated cells were analysed by flow cytometry. RESULTS: Survival of the auditory neurons in the dissociated cells was significantly increased by addition of BDNF, NT-3, and 25K. The effect of 25 mM K+ on neuronal survival showed the highest in the experimental conditions. BDNF dramatically increased the neurite length compared with those under other conditions. After immunomagnetic sorting in dissociated cultures, spiral ganglion neurons were shown to contain 50% of the fluorescently labeled positive cells. CONCLUSIONS: Neurotrophins (BDNF, NT-3) and depolarization by 25 mM K+ were essential trophic factors for postnatal auditory neurons and BDNF stimulated neuritogenesis in cultured spiral ganglion neurons. The immunomagnetic cell sorting method is not appropriate for collecting pure neural cells from the dissociated cells of spiral ganglia (50% purity).

Calcium Antagonist-like Action of Antidepressants Including Sertraline in PCl2 Cells / 신경정신의학

It has been known that antidepressants have calcium antagonist-like action in neuronal tissues. However, their mechanisms are still obscure. For the study of neurochemical machanism of antidepressants, the authors examined the effects of antidepressants(1-100 microM ) on the intracellular Ca2+ concentration ([Ca2+]i) and the membrane potential in PCl2 cells using fluorescent dyes, fura-2/AM and bisoxonol, respectively. The results were as follows : 1) Sertraline, a selective serotonin reuptake inhibitor (SSRI), inhibited the increment of [Ca2+]i induced by high 60 mM KCI and 100 microM ATP with an IC50 value of 2.5 microM and 5.4 microM, respectively. 2) SSRIs(sertraline, paroxetine and fluoxetine) and tricyclic antidepressants(imipramine and amitriptyline) had strong effects on the inhibition of both voltage-dependent Ca2+ channel and receptor-dependent Ca2+ channel, whereas atypical antidepressant(trazodone) and MAO inhibitor(moclobemide) had lisle effects. 3) Sertraline itself depolarized the membrane potential in a sustained manner depending on its own concentration and it also increased the basal level of [Ca2+]i. 4) The increment of [Ca2+]i might be induced partly by the release from the intracellular calcium store, but mostly induced by the calcium transport through membrane. 5) Among those antidepressants tested, sertraline was the most potent one. Other SSRIs(paroxetine and fluoxetine) and tricyclic antidepressants(imipramine and amitriptyline) were moderately potent. Atypical antidepressant(trazodone) had little effects, and MAO inhibitor (moclobemide) had no effect on the depolarization. 6) External application of ATP induced temporary depolarization. This effect was blocked by prior treatment with sertraline with an IC50 value of 30 microM. 7) The increment of [Ca2+]i through voltage-dependent Ca2+ channel was almost inhibited by a selective calcium channel blocker(nimodipine). However, the ATP-induced increment of [Ca2+]i was partially inhibited by nimodipine. These inhibitory effects were potentiated by the addition of sertraline. In the light of these results, it is likely that SSRIs and tricyclic antidepressants could show the blocking effects on both voltage-dependent and receptor-dependent calcium channel by depolarizing neuronal cell membrane potential in a sustained manner and by increasing intracellular free calcium level.

Changes in cytosolic Ca2+ but not in cGMP contents may be more important to nitric oxide-mediated relaxation in depolarized vascular smooth muscle

Nitric oxide (NO)-mediated relaxation in vascular smooth muscle involves not only activation of guanylate cyclase but also hyperpolarization of the membrane. It has been shown that depolarization decreases the (Ca2+) sensitivity of myosin light chain kinase in arterial smooth muscle, and nitric oxide (NO)-mediated relaxation was attenuated in this situation. However, why potassium inhibits or attenuates the action of EDRF/NO is not clear. Therefore, we investigated the magnitude of relaxation and cGMP contents using measures known to release NO, such as photorelaxation, photo activated NO-mediated relaxation, and NO-donor (SNP)-mediated relaxation in porcine coronary arterial rings in which contractile conditions were made by different degree of depolarization, i.e., contraction in response to U46619 or U46619 plus KCl. In all cases, the magnitude of relaxation was significantly greater (P<0.05) in U46619-contracted rings than in U46619+KCl-contracted ones. Although accumulation of cGMP was evident with three measures employed in the present study, no difference was found in cGMP contents between U46619 and U46619+KCl conditions, indicating that the diminished relaxation in KCl containing solution is cGMP-independent mechanism(s). To understand this further, cytosolic Ca2+ changes due to NO were compared in rat thoracic aorta by exploiting photoactivated NO using streptozotocin (STZ) that was contracted with either NE or KCl. Fura-3 (Ca)cyt signal caused by NO was small and transient in high K+-, but large and sustained in NE-contracted aorta. The inhibitory potency of STZ expressed in terms Of IC50 was 5.14 and 3.88 gM in NE and in high K+, respectively. These results suggest that modification of the cellular mobilization of Ca2+ rather than cGMP levels may be an important mechanism for the NO-mediated relaxation when vascular membrane is depolarized, such as atherosclerosis and hypertension.

Mechanism of Low K+-induced Depolarization in Mammalian Cardiac Muscle

The membrane permeability to potassium at a resting state is greater than to any other ions and the maintenance of resting membrane potential is largely dependent on K+ concentration of outside medium (Hodgkin and Horowicz 1959), i.e. an increase of K+ concentration of medium induces a depolarization, vice versa. However, on the contrary to this prediction, in some mammalian heart muscle a reduction of external K+ concentration induces a depolarization of membrane potential rather than a hyperpolarization (Vassalle 1965). In this study it was aimed to elucidate the possible mechanism of spontaneous depolarization induced by low external K+ in canine Purkinje fibers. The membrane potential was constantly recorded while components of cations in the bathing medium were replaced one by one by equimolar sucrose until the low K+ induced depolarization was blocked. The results are summarized as follows; The membrane potential of canine Purkinje fibers was spontaneously depolarized by low external K+, and the magnitude of depolarization was not affected by verapamil TEA, and a partial replacement of external Na+ and Ca2+ with choline chloride. But the membrane potential was hyperpolarized only when the all external cations were substitued with sucrose; and this hyperpolarization was disappeared again by substitution of sucrose with choline chloride. From these results, it may be concluded that the depolarization induced by low external K+ in canine Purkinje fibers is due to the nonspecific increase of membrane permeability to external cations and/or combinations with decreased K+ conductance.

INFLUENCES OF CONDITIONING STIMULI OF PERIPHERAL NERVE ON C-FIBRE AFFERENT TERMINAL EXCITABILITY IN SPINAL TOADS / 西安交通大学学报(医学版)

The antidromic C waves elicited by stimulating the entry zone of the dorsal root were recorded in spinal toads. Influences if conditioning stimuli in 60 T from sciatic nerve on antidromic C waves were observed. The conditioning stimuli produced marked increace in the excitability of the C-afferent terminals. The increased excitability possessed two phases. The results indicat that periphiral primary afferent A and C-fibres can produce presynaptic inhibition in C-fibre terminals.