scholarly journals Comparative Studies on the Inhibitory Effects of Calcium Antagonists on Cytosolic Ca2+ Levels Increased by High-Potassium or Glutamate in Cultured Rat Cerebellar Granule Cells

1993 ◽  
Vol 61 (4) ◽  
pp. 267-276 ◽  
Author(s):  
Xiang-Qian Zhang ◽  
Yasuo Watanabe ◽  
Masatoshi Ohnishi ◽  
Tsuyoshi Baba ◽  
Takeshi Shibuya
Keyword(s):  
Calcium Antagonists ◽  
Comparative Studies ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Inhibitory Effects ◽  
High Potassium ◽  
Cerebellar Granule

scholarly journals Bone Morphogenetic Protein-6 Promotes Cerebellar Granule Neurons Survival by Activation of the MEK/ERK/CREB Pathway

2009 ◽  
Vol 20 (24) ◽  
pp. 5051-5063 ◽  
Author(s):  
Bruna Barneda-Zahonero ◽  
Alfredo Miñano-Molina ◽  
Nahuai Badiola ◽  
Rut Fadó ◽  
Xavier Xifró ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Neuroprotective Effect ◽  
High Potassium ◽  
Cerebellar Granule ◽  
Low Potassium ◽  
Creb Pathway

Bone morphogenetic proteins (BMPs) have been implicated in the generation and postnatal differentiation of cerebellar granule cells (CGCs). Here, we examined the eventual role of BMPs on the survival of these neurons. Lack of depolarization causes CGC death by apoptosis in vivo, a phenomenon that is mimicked in vitro by deprivation of high potassium in cultured CGCs. We have found that BMP-6, but not BMP-7, is able to block low potassium–mediated apoptosis in CGCs. The neuroprotective effect of BMP-6 is not accompanied by an increase of Smad translocation to the nucleus, suggesting that the canonical pathway is not involved. By contrast, activation of the MEK/ERK/CREB pathway by BMP-6 is necessary for its neuroprotective effect, which involves inhibition of caspase activity and an increase in Bcl-2 protein levels. Other pathways involved in the regulation of CGC survival, such as the c-Jun terminal kinase and the phosphatidylinositol 3-kinase (PI3K)-Akt/PKB, were not affected by BMP-6. Moreover, failure of BMP-7 to activate the MEK/ERK/CREB pathway could explain its inability to protect CGCs from low potassium–mediated apoptosis. Thus, this study demonstrates that BMP-6 acting through the noncanonical MEK/ERK/CREB pathway plays a crucial role on CGC survival.

Functional characterization of the effect of nimodipine on the calcium current in rat cerebellar granule cells

1995 ◽  
Vol 73 (3) ◽  
pp. 1169-1180 ◽  
Author(s):  
C. Marchetti ◽  
C. Amico ◽  
C. Usai
Keyword(s):  
Calcium Current ◽  
Time Course ◽  
Lipid Membrane ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Functional Characterization ◽  
Duration Of Treatment ◽  
High Potassium ◽  
Cerebellar Granule ◽  
Internal Calcium

1. We investigated the effect of nimodipine on the calcium current in dissociated cerebellar granule cells from 8-day-old rats. We measured the whole cell current and the depolarization-induced internal calcium elevation in Fura2-loaded cells exposed to high-potassium solutions. 2. Nimodipine maximally depressed the peak calcium current from holding potential (Vh) = -80 mV by 25% and the inactivation resistant residual current from Vh = -50 mV by 44%. The nimodipine-sensitive current had the same amplitude under both conditions and the half-maximal inhibition concentration (IC50) was close to 50 nM. 3. In contrast to other components of the calcium current, the nimodipine-sensitive current did not inactivate significantly during 1-s depolarization and it was weakly sensitive to the holding potential and to depolarizing conditioning prepulses. The effect of nimodipine was higher on the current elicited by small depolarizations and the current at -30 mV was depressed by < or = 70%. Depolarizing prepulses enhanced the effect of 1 nM (but not that of 1 microM) nimodipine. 4. In Fura2-loaded cells, nimodipine strongly antagonized the internal calcium rise due to superfusion with 15-75 mM potassium. The effect was significantly more potent on the internal calcium rise determined by lower depolarizations, with 80% inhibition of the peak response to 25 mM KCl. The dose dependence of this depression was best approximated by a two-site curve with IC50(1) = 0.27 nM and IC50(2) = 65 nM. The time course of recovery was dependent on the duration of treatment, suggesting a close interaction between nimodipine and the lipid membrane. 5. The effect of 1 microM nimodipine was not influenced by predepolarizations determined by treatments with calcium-free elevated potassium solutions, but when doses as low as 1 nM were applied the fast decay of the calcium level suggested a voltage dependence of the effect. Nimodipine also depressed < or = 90% of the plateau phase of the depolarization-induced internal calcium rise at different depolarizations. 6. Incubation in omega-conotoxin, fraction GVIA (5 microM) did not cause any significant decrease in the calcium response, whereas omega-agatoxin, fraction IVA (0.5 microM) depressed the calcium peak by 40-60% and its effect was additive with that of nimodipine. 7. We conclude that the nimodipine-sensitive current is a persistent, inactivation-resistant current that activates at a membrane potential lower than the other components and is likely to be responsible for the elevation of calcium determined by nonovershooting, prolonged depolarizations in these cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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