Potassium Channel Antagonists Influence Porcine Granulosa Cell Proliferation, Differentiation, and Apoptosis1

Manikkam, Mohan; Li, Yan; Mitchell, Brianna M.; Mason, Diane; Freeman, Lisa C.

doi:10.1095/biolreprod67.1.88

Cited by 33 publications

(19 citation statements)

References 48 publications

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“…In agreement with emerging evidence that excessive K + efflux and depletion of intracellular K + act as key steps in the apoptotic process [17][18][19][20], K + channel blockers, such as tetraethylammonium (TEA) and clofilium, attenuate apoptosis in central neurons and peripheral cells [17,[21][22][23][24]. On the other hand, clofilium causes apoptosis in human promyelocytic leukemia (HL-60) cells [25] and murine B cell lymphoma CH27 cells [26].…”

Section: Introductionsupporting

confidence: 77%

Inhibitory Effects of Clofilium on Membrane Currents Associated with Ca2+ Channels, NMDA Receptor Channels and Na+, K+-ATPase in Cortical Neurons

et al. 2005

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The class III antiarrhythmic agent 4-chloro-N,N-diethyl-N-heptyl-benzene butanaminium (clofilium) is known as a K⁺ channel open-channel blocker and has either anti- or proapoptotic property due to undefined mechanisms. Based on the evidence that neuronal viability is largely, sometimes critically, affected by voltage- and ligand-gated Ca²⁺ channels and the Na⁺, K⁺-ATPase, we tested the hypothesis that clofilium might additionally act on Ca²⁺ permeable ion channels and the Na⁺, K⁺-ATPase. Membrane currents associated with activities of voltage-gated Ca²⁺ channels, N-methyl-D-aspartate (NMDA) receptor channels and Na⁺, K⁺-ATPase were recorded using whole-cell recordings in cultured murine cortical neurons. Clofilium (0.1–100 µmol/l) inhibited high voltage-activated Ca²⁺ currents in concentration- and use-dependent manners. Clofilium acted as a potent antagonist of NMDA receptor channels, preferably blocked the NMDA steady-state current at a low concentration (0.1 µmol/l). At concentrations of >100 µmol/l, clofilium blocked both peak and steady-state NMDA currents in a voltage-independent manner. Clofilium also inhibited the Na⁺, K⁺-ATPase current with an IC₅₀ of 7.5 µmol/l. Our data suggest that the pharmacological action of clofilium is far more complex than recognized before; the multiple actions of clofilium on membrane conductance may explain its diverse effects on cellular events and cell viability.

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Section: Introductionsupporting

confidence: 77%

Inhibitory Effects of Clofilium on Membrane Currents Associated with Ca2+ Channels, NMDA Receptor Channels and Na+, K+-ATPase in Cortical Neurons

et al. 2005

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“…This suggests that distinct potassium channels or potassium transport mechanisms may be involved depending on the cell type or stimulus used to induce apoptosis (Table 1). Manikkam et al [36] demonstrated this diversity in potassium channels where different effects on cellular proliferation, differentiation, and apoptosis occurred depending on the specific potassium antagonists applied to porcine granulosa cells. Dupart et al [37] showed that diverse types of K + channels are differently modified in response to reactive oxygen species (ROS), a known stimulus of apoptosis in many cell types.…”

Section: Potassium Channels In Apoptosismentioning

confidence: 99%

Cell shrinkage and monovalent cation fluxes: Role in apoptosis

Bortner

Cidlowski

2007

Archives of Biochemistry and Biophysics

230

193

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The loss of cell volume or cell shrinkage has been a morphological hallmark of the programmed cell death process known as apoptosis. This isotonic loss of cell volume has recently been term apoptotic volume decrease or AVD to distinguish it from inherent volume regulatory responses that occurs in cells under anisotonic conditions. Recent studies examining the intracellular signaling pathways that result in this unique cellular characteristic have determined that a fundamental movement of ions, particularly monovalent ions, underlie the AVD process and plays an important role on controlling the cell death process. An efflux of intracellular potassium was shown to be a critical aspect of the AVD process, as preventing this ion loss could protect cells from apoptosis. However, potassium plays a complex role as a loss of intracellular potassium has also been shown to be beneficial to the health of the cell. Additionally, the mechanisms that a cell employs to achieve this loss of intracellular potassium vary depending on the cell type and stimulus used to induce apoptosis, suggesting multiple ways exist to accomplish the same goal of AVD. Additionally, sodium and chloride have been shown to play a vital role during cell death in both the signaling and control of AVD in various apoptotic model systems. This review examines the relationship between this morphological change and intracellular monovalent ions during apoptosis.

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“…Notwithstanding this interaction, cumulus cells and oocytes do maintain different membrane potentials in spite of the existence of low resistance channels, such as gap junctions [Emery et al 2001]. Depolarization of granulosa cells was addressed as an essential feature of follicular maturation; this hypothesis is supported by the finding that differential granulosa cell proliferation, steroidogenic capability, and apoptosis can be influenced by selective antagonism of granulosa cell potassium channels [Manikkam et al 2002]. The interaction between cumulus cells and the oocyte decreases at the end of maturation, together with cumulus expansion and the breaking of heterologous gap junction communications.…”

Section: Mammalsmentioning

confidence: 99%

Ion currents modulating oocyte maturation in animals

Tosti

Boni

Gallo

et al. 2013

Systems Biology in Reproductive Medicine

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Growing oocytes are arrested at the first prophase of meiosis which is morphologically identified by the presence of a large and vesicular nucleus, called the germinal vesicle. The dissolution of the germinal vesicle marks the resumption of meiosis during which the oocyte undergoes massive modifications up to the second meiotic block, which is removed at fertilization. The interval between the first and the second meiotic block is defined as maturation and the events occurring during this period are crucial for ovulation, fertilization, and embryo development. Oocytes are excitable cells that react to stimuli by modifying their electrical properties as a consequence of ion currents flowing through ion channels on the plasma membrane. These electrical changes have been largely described at fertilization whereas little information is available during oocyte maturation. The aim of this review is to give an overview on the involvement of ion channels and ion currents during oocyte maturation in species from invertebrates to mammals. The results summarized here point to the possible functional role of ion channels underlying oocyte growth and maturation.

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Potassium Channel Antagonists Influence Porcine Granulosa Cell Proliferation, Differentiation, and Apoptosis1

Cited by 33 publications

References 48 publications

Inhibitory Effects of Clofilium on Membrane Currents Associated with Ca<sup>2+</sup> Channels, NMDA Receptor Channels and Na<sup>+</sup>, K<sup>+</sup>-ATPase in Cortical Neurons

Inhibitory Effects of Clofilium on Membrane Currents Associated with Ca<sup>2+</sup> Channels, NMDA Receptor Channels and Na<sup>+</sup>, K<sup>+</sup>-ATPase in Cortical Neurons

Cell shrinkage and monovalent cation fluxes: Role in apoptosis

Ion currents modulating oocyte maturation in animals

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