[43] Overview of toxins and drugs as tools to study excitable membrane ion channels: I. Voltage-activated channels

Narahashi, Toshio; Herman, Martin D.

doi:10.1016/0076-6879(92)07045-p

Cited by 35 publications

(20 citation statements)

References 155 publications

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“…3C). Moreover, after EP stimulation, addition of nickel, a calcium channel blocker (28), induced a return of [Ca 2ϩ ] i to its basal value (Fig. 3D).…”

Section: Resultsmentioning

confidence: 99%

Nuclear and cytoplasmic free calcium level changes induced by elastin peptides in human endothelial cells

Faury

Usson

Robert‐Nicoud

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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The extracellular matrix protein ''elastin'' is the major component of elastic fibers present in the arterial wall. Physiological degradation of elastic fibers, enhanced in vascular pathologies, leads to the presence of circulating elastin peptides (EP). EP have been demonstrated to inf luence cell migration and proliferation. EP also induce, at circulating pathophysiological concentrations (and not below), an endothelium-and NO-dependent vasorelaxation mediated by the 67-kDa subunit of the elastin-laminin receptor. Here, by using the techniques of patch-clamp, spectrof luorimetry and confocal microscopy, we demonstrate that circulating concentrations of EP activate low specificity calcium channels on human umbilical venous endothelial cells, resulting in increase in cytoplasmic and nuclear free calcium concentrations. This action is independent of phosphoinositide metabolism. Furthermore, these effects are inhibited by lactose, an antagonist of the elastin-laminin receptor, and by cytochalasin D, an actin microfilament depolymerizer. These observations suggest that EP-induced signal transduction is mediated by the elastin-laminin receptor via coupling of cytoskeletal actin microfilaments to membrane channels and to the nucleus. Because vascular remodeling and carcinogenesis are accompanied by extracellular matrix modifications involving elastin, the processes here described could play a role in the elastin-laminin receptor-mediated cellular migration, differentiation, proliferation, as in atherogenesis, and metastasis formation.Elastic fibers in arteries, pulmonary alveolar septa, certain ligaments and skin are normally subjected to stretching. In vascular walls, elastic fibers organize into concentric sheets that endow the arteries with resiliency. In physiological conditions, elastin is synthesized only during the late stages of gestation and early infancy. Although elastin is a stable protein (1), a slow and regular elastin degradation mediated by specialized proteases-the elastases-occurs, contributing to the age-dependent increase in vessel stiffness. This process leads to the presence of elastin peptides (EP) in the circulation (10) (2, 3), increased in some vascular pathologies, as for instance arteriosclerosis (3, 4). EP influence cell migration (5) and proliferation (6) and, in adult rats, EP induce, at circulating concentrations (and not below), an endothelium-dependent vasodilation mediated by NO (7). EP act via binding to the 67-kDa subunit of the high affinity elastin-laminin receptor, present on the cell membranes of the vascular endothelial cells and on numerous other cell types, including arterial medial smooth muscle cells (8-11). Moreover, activation of the 67-kDa subunit of the elastin-laminin receptor also produces a variety of biological reactions, as for instance modifying cell migration (12), differentiation (13), proliferation (6), and enhancing metastatic potential of transformed cells (14,15). The presence and density of the 67-kDa subunit on transformed cell membranes was clai...

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“…3C). Moreover, after EP stimulation, addition of nickel, a calcium channel blocker (28), induced a return of [Ca 2ϩ ] i to its basal value (Fig. 3D).…”

Section: Resultsmentioning

confidence: 99%

Nuclear and cytoplasmic free calcium level changes induced by elastin peptides in human endothelial cells

Faury

Usson

Robert‐Nicoud

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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“…A mere extrapolation of the results obtained with muscular and cardiac Na + channels to neuronal channels does not seem justified as Na + channels in nervous and muscular tissue are encoded by different genes and have different pharmacological properties [18].…”

Section: Resultsmentioning

confidence: 99%

Excitatory sodium currents of NH15-CA2 neuroblastoma x glioma hybrid cells are differently affected by interleukin-2 and interleukin-1β

Hamm

Rüdel

Brinkmeier

1996

Pfl�gers Archiv European Journal of Physiology

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The neuroblastoma x glioma hybrid cell line NH15-CA2 was used to test the effects of two interleukins on neuronal Na+ channels. The cells were cultured in the presence of dibutyryl cAMP and retinoic acid, which yielded a high expression of Na+ channels so that the cells were excitable. Na+ currents were triggered and recorded in the whole-cell recording mode. Comparison of the effects of tetrodotoxin and mu-conotoxin established that the expressed Na+ channels were of the neuronal type. Bath-applied recombinant human interleukin-2 (rIL-2) had a reversible inhibitory effect on the Na+ currents, although to a lesser extent than on muscular Na+ currents (more than 1000 U/ml required for 50% block in NH15-CA2 cells vs 500 U/ml in myoballs). The current/voltage relationship was not affected by the presence of rIL-2, but the steady-state inactivation curve was shifted by -7.7 +/- 4.8 mV (mean +/- SD, n=18). Recombinant human interleukin-1beta (rIL-1beta), applied at 1000 U/ml, showed an inhibitory effect on the Na+ currents in about one-third of the cells tested. The mechanism of inhibition was different from that of rIL-2, as rIL-1beta seemed to cause a block without affecting voltage dependence or kinetics of the channels.

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“…The demonstration that methoxyverapamil inhibited the E 2 -BSA-induced stimulation of Ca 2ϩ uptake indicated that E 2 -BSA stimulates Ca 2ϩ uptake through L-type calcium channels. Calcium channels may be directly activated by G protein(s) (Dolphin, 1991) or indirectly by cAMP-dependent phosphorylation, a process that uses cAMP-dependent protein kinase A (Narahashi and Herman, 1992). Estrogenic hormones are found to increase cAMP in target breast cancer and uterine cells in culture and in the intact uterus in vivo (Aronica et al, 1994).…”

Section: Discussionmentioning

confidence: 98%

Estradiol-17?-BSA stimulates Ca2+ uptake through nongenomic pathways in primary rabbit kidney proximal tubule cells: Involvement of cAMP and PKC

2000

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The effect of estradiol-17beta-BSA (E(2)-BSA) on Ca(2+) uptake and its related signal pathways were examined in the primary cultured rabbit kidney proximal tubule cells. E(2)-BSA (10(-9) M) significantly stimulated Ca(2+) uptake from 2 h by 13% and at 8 h by 35% as compared to control, respectively. This stimulatory effect of E(2)-BSA was not inhibited by tamoxifen (10(-8) M, an intracellular estrogen receptor antagonist), actinomycin D (10(-7) M, a transcription inhibitor), and cycloheximide (4 x 10(-5) M, a protein synthesis inhibitor). However, E(2)-BSA-induced stimulation of Ca(2+) uptake was blocked by methoxyverapamil (10(-6) M, an L-type calcium channel blocker) and 5-(N-ethyl-N-isopropyl)-amiloride (10(-5) M, a Na(+)/H(+) antiporter blocker). These results suggest that E(2)-BSA stimulates Ca(2+) uptake through nongenomic pathways. Thus, we investigated which signal pathways were related to E(2)-BSA-induced stimulation of Ca(2+) uptake. 8-Br-cAMP (10(-6) M) alone increased Ca(2+) uptake by 22% compared to control. When E(2)-BSA combined with 8-Br-cAMP, Ca(2+) uptake was not significantly stimulated compared to E(2)-BSA. SQ 22536 (10(-6) M, an adenylate cyclase inhibitor) and myristoylated protein kinase A inhibitor amide 14-22 (10(-6) M, a protein kinase A inhibitor) blocked E(2)-BSA-induced stimulation of Ca(2+) uptake and E(2)-BSA also increased cAMP generation by 26% of that of control. In addition, TPA (0.02 ng/ml, an artificial PKC promoter) stimulated the Ca(2+) uptake by 14%, and the cotreatment of TPA and E(2)-BSA did not significantly stimulate Ca(2+) uptake compared to E(2)-BSA. E(2)-BSA-induced stimulation of Ca(2+) uptake was blocked by U 73122 (10(-6) M, a phospholipase C inhibitor) or bisindolylmaleimide I (10(-6) M, a protein kinase C inhibitor). Indeed, E(2)-BSA stimulated PKC activity by 26%. In conclusion, E(2)-BSA (10(-9) M) stimulated Ca(2+) uptake by nongenomic action, which is mediated by cAMP and PKC pathways.

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[43] Overview of toxins and drugs as tools to study excitable membrane ion channels: I. Voltage-activated channels

Cited by 35 publications

References 155 publications

Nuclear and cytoplasmic free calcium level changes induced by elastin peptides in human endothelial cells

Nuclear and cytoplasmic free calcium level changes induced by elastin peptides in human endothelial cells

Excitatory sodium currents of NH15-CA2 neuroblastoma x glioma hybrid cells are differently affected by interleukin-2 and interleukin-1β

Estradiol-17?-BSA stimulates Ca2+ uptake through nongenomic pathways in primary rabbit kidney proximal tubule cells: Involvement of cAMP and PKC

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