Depolarization — Transcription coupling in excitable cells

Plasmalemmal transport of magnesium in excitable cells

Frontiers in Bioscience ◽

10.2741/rasgado ◽

2000 ◽

Vol 5 (1) ◽

pp. d866 ◽

Cited By ~ 6

Author(s):

Hector Rasgado-Flores

Keyword(s):

Excitable Cells

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Volcano-Shaped Scanning Probe Microscopy Probe for Combined Force-Electrogram Recordings from Excitable Cells

Nano Letters ◽

10.1021/acs.nanolett.0c01319 ◽

2020 ◽

Vol 20 (6) ◽

pp. 4520-4529

Author(s):

B. X. E. Desbiolles ◽

M. T. M Hannebelle ◽

E. de Coulon ◽

A. Bertsch ◽

S. Rohr ◽

...

Keyword(s):

Scanning Probe Microscopy ◽

Scanning Probe ◽

Excitable Cells ◽

Probe Microscopy

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Roles of Microglial Ion Channel in Neurodegenerative Diseases

Journal of Clinical Medicine ◽

10.3390/jcm10061239 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1239

Author(s):

Alexandru Cojocaru ◽

Emilia Burada ◽

Adrian-Tudor Bălșeanu ◽

Alexandru-Florian Deftu ◽

Bogdan Cătălin ◽

...

Keyword(s):

Ion Channels ◽

Neurodegenerative Diseases ◽

Excitable Cells ◽

Proton Channels ◽

Voltage Gated ◽

Cellular Processes ◽

Pathological Conditions ◽

The Common ◽

Transient Receptor ◽

The Impact

As the average age and life expectancy increases, the incidence of both acute and chronic central nervous system (CNS) pathologies will increase. Understanding mechanisms underlying neuroinflammation as the common feature of any neurodegenerative pathology, we can exploit the pharmacology of cell specific ion channels to improve the outcome of many CNS diseases. As the main cellular player of neuroinflammation, microglia play a central role in this process. Although microglia are considered non-excitable cells, they express a variety of ion channels under both physiological and pathological conditions that seem to be involved in a plethora of cellular processes. Here, we discuss the impact of modulating microglia voltage-gated, potential transient receptor, chloride and proton channels on microglial proliferation, migration, and phagocytosis in neurodegenerative diseases.

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Regulation of Store-Operated Ca2+ Entry by SARAF

Cells ◽

10.3390/cells10081887 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1887

Author(s):

Inbal Dagan ◽

Raz Palty

Keyword(s):

Molecular Mechanisms ◽

Feedback Mechanism ◽

Cellular Biology ◽

Excitable Cells ◽

Major Pathway ◽

Negative Feedback Mechanism ◽

Crac Channels ◽

Dependent Inactivation ◽

Crac Channel ◽

The One

Calcium (Ca2+) signaling plays a dichotomous role in cellular biology, controlling cell survival and proliferation on the one hand and cellular toxicity and cell death on the other. Store-operated Ca2+ entry (SOCE) by CRAC channels represents a major pathway for Ca2+ entry in non-excitable cells. The CRAC channel has two key components, the endoplasmic reticulum Ca2+ sensor stromal interaction molecule (STIM) and the plasma-membrane Ca2+ channel Orai. Physical coupling between STIM and Orai opens the CRAC channel and the resulting Ca2+ flux is regulated by a negative feedback mechanism of slow Ca2+ dependent inactivation (SCDI). The identification of the SOCE-associated regulatory factor (SARAF) and investigations of its role in SCDI have led to new functional and molecular insights into how SOCE is controlled. In this review, we provide an overview of the functional and molecular mechanisms underlying SCDI and discuss how the interaction between SARAF, STIM1, and Orai1 shapes Ca2+ signaling in cells.

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Characterization of Direct Perturbations on Voltage-Gated Sodium Current by Esaxerenone, a Nonsteroidal Mineralocorticoid Receptor Blocker

Biomedicines ◽

10.3390/biomedicines9050549 ◽

2021 ◽

Vol 9 (5) ◽

pp. 549

Author(s):

Wei-Ting Chang ◽

Sheng-Nan Wu

Keyword(s):

Mineralocorticoid Receptor ◽

Sodium Current ◽

Ionic Currents ◽

Antagonistic Effect ◽

Gh3 Cells ◽

Excitable Cells ◽

Voltage Gated ◽

Ic50 Value ◽

Low Threshold

Esaxerenone (ESAX; CS-3150, Minnebro®) is known to be a newly non-steroidal mineralocorticoid receptor (MR) antagonist. However, its modulatory actions on different types of ionic currents in electrically excitable cells remain largely unanswered. The present investigations were undertaken to explore the possible perturbations of ESAX on the transient, late and persistent components of voltage-gated Na+ current (INa) identified from pituitary GH3 or MMQ cells. GH3-cell exposure to ESAX depressed the transient and late components of INa with varying potencies. The IC50 value of ESAX required for its differential reduction in peak or late INa in GH3 cells was estimated to be 13.2 or 3.2 μM, respectively. The steady-state activation curve of peak INa remained unchanged during exposure to ESAX; however, recovery of peak INa block was prolonged in the presence 3 μM ESAX. In continued presence of aldosterone (10 μM), further addition of 3 μM ESAX remained effective at inhibiting INa. ESAX (3 μM) potently reversed Tef-induced augmentation of INa. By using isosceles-triangular ramp pulse with varying durations, the amplitude of persistent INa measured at high or low threshold was enhanced by the presence of tefluthrin (Tef), in combination with the appearance of the figure-of-eight hysteretic loop; moreover, hysteretic strength of the current was attenuated by subsequent addition of ESAX. Likewise, in MMQ lactotrophs, the addition of ESAX also effectively decreased the peak amplitude of INa along with the increased current inactivation rate. Taken together, the present results provide a noticeable yet unidentified finding disclosing that, apart from its antagonistic effect on MR receptor, ESAX may directly and concertedly modify the amplitude, gating properties and hysteresis of INa in electrically excitable cells.

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Synthesis and Characterization of Store-Operated Calcium Entry Inhibitors Active in the Submicromolar Range

International Journal of Molecular Sciences ◽

10.3390/ijms21249777 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9777

Author(s):

Camille Le Guilcher ◽

Tomas Luyten ◽

Jan B. Parys ◽

Mathieu Pucheault ◽

Olivier Dellis

Keyword(s):

Cell Activation ◽

Interleukin 2 ◽

Calcium Entry ◽

Ip3 Receptors ◽

Excitable Cells ◽

Cellular Targets ◽

Entry Inhibitors ◽

The Past ◽

Store Operated Calcium Entry

The store-operated calcium entry, better known as SOCE, forms the main Ca2+ influx pathway in non-excitable cells, especially in leukocytes, where it is required for cell activation and the immune response. During the past decades, several inhibitors were developed, but they lack specificity or efficacy. From the non-specific SOCE inhibitor 2-aminoethyl diphenylborinate (2-APB), we synthetized 16 new analogues by replacing/modifying the phenyl groups. Among them, our compound P11 showed the best inhibitory capacity with a Ki ≈ 75 nM. Furthermore, below 1 µM, P11 was devoid of any inhibitory activity on the two other main cellular targets of 2-APB, the IP3 receptors, and the SERCA pumps. Interestingly, Jurkat T cells secrete interleukin-2 under phytohemagglutinin stimulation but undergo cell death and stop IL-2 synthesis when stimulated in the presence of increasing P11 concentrations. Thus, P11 could represent the first member of a new and potent family of immunosuppressors.

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Stochastic Spatial Heterogeneity in Activities of H+-ATP-ases in Electrically Connected Plant Cells Decreases Threshold for Cooling-Induced Electrical Responses

International Journal of Molecular Sciences ◽

10.3390/ijms22158254 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8254

Author(s):

Ekaterina Sukhova ◽

Daria Ratnitsyna ◽

Vladimir Sukhov

Keyword(s):

Spatial Heterogeneity ◽

Action Potentials ◽

Higher Plants ◽

Electrical Response ◽

Plant Cells ◽

Excitable Cells ◽

Molecular Transporters ◽

Positive Shift ◽

Stochastic Heterogeneity ◽

Electrical Responses

H+-ATP-ases, which support proton efflux through the plasma membrane, are key molecular transporters for electrogenesis in cells of higher plants. Initial activities of the transporters can influence the thresholds of generation of electrical responses induced by stressors and modify other parameters of these responses. Previously, it was theoretically shown that the stochastic heterogeneity of individual cell thresholds for electrical responses in a system of electrically connected neuronal cells can decrease the total threshold of the system (“diversity-induced resonance”, DIR). In the current work, we tested a hypothesis about decreasing the thresholds of generation of cooling-induced electrical responses in a system of electrically connected plant cells with increasing stochastic spatial heterogeny in the initial activities of H+-ATP-ases in these cells. A two-dimensional model of the system of electrically connected excitable cells (simple imitation of plant leaf), which was based on a model previously developed in our works, was used for the present investigation. Simulation showed that increasing dispersion in the distribution of initial activities of H+-ATP-ases between cells decreased the thresholds of generation of cooling-induced electrical responses. In addition, the increasing weakly influenced the amplitudes of electrical responses. Additional analysis showed two different mechanisms of the revealed effect. The increasing spatial heterogeneity in activities of H+-ATP-ases induced a weak positive shift of the membrane potential at rest. The shift decreased the threshold of electrical response generation. However, the decreased threshold induced by increasing the H+-ATP-ase activity heterogeneity was also observed after the elimination of the positive shift. The result showed that the “DIR-like” mechanism also participated in the revealed effect. Finally, we showed that the standard deviation of the membrane potentials before the induction of action potentials could be used for the estimation of thresholds of cooling-induced plant electrical responses. Thus, spatial heterogeneity in the initial activities of H+-ATP-ases can be a new regulatory mechanism influencing the generation of electrical responses in plants under actions of stressors.

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