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Published on: August 14, 2015
MEK inhibitor PD98059 acutely inhibits synchronized spontaneous Ca2+ oscillations in cultured hippocampal networks
Yan-fang Rui1, Zhao-hui Sun, Jia-ping Gu
1Department of Biological Science and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
Aim:
To investigate the changes in synchronized spontaneous Ca2+ oscillations induced by mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 at different concentrations in cultured hippocampal network.
Methods:
Hippocampal neurons in culture for 1-2 weeks were used for this study. Spontaneous synaptic activities of these hippocampal neurons were examined by Ca2+ imaging using calcium-sensitive dye. MEK inhibitor PD98059 (10, 30, and 60 micromol/L) and SB202474 (10 and 60 micromol/L), a negative control for mitogen-activated protein kinase (MAPK) cascade study, were applied to the cells under the microscope while imaging was taking place.
Results:
PD98059 at a lower concentration of 10 micromol/L had little effect on the Ca2+ oscillation. At the higher concentration of 30 micromol/L, 5 min after application of PD98059, the spike frequency was decreased to 25.38% +/-7.40% (mean+/-SEM, n=16, P<0.01 vs medium control) of that of the control period. At an even higher concentration of 60 micromol/L, 5 min after application of PD98059, the spike frequency was decreased to 14.53%+/-5.34% (mean+/-SEM, n=16, P< 0.01 vs medium control) of that of the control period. The spike amplitude underwent a corresponding decrease. However, the negative control SB202474 at concentrations of 10 and 60 micromol/L had little inhibition effect on the Ca2+ oscillation.
Conclusion:
These results indicate that PD98059 inhibits synchronized spontaneous Ca2+ oscillation through inhibition of MEK, which hints that the MAPK cascade is required to maintain synchronized spontaneous Ca2+ oscillation.
Insights
Mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 reduces synchronized spontaneous Ca2+ oscillations in hippocampal networks. This suggests the mitogen-activated protein kinase (MAPK) cascade is essential for maintaining these oscillations.
Area of Science:
- Neuroscience
- Cellular Biology
- Pharmacology
Background:
- Synchronized spontaneous Ca2+ oscillations are crucial for neuronal network function.
- The mitogen-activated protein kinase (MAPK) cascade plays a role in neuronal signaling.
Purpose of the Study:
- To investigate the effect of the MEK inhibitor PD98059 on Ca2+ oscillations in cultured hippocampal neurons.
- To determine the role of the MAPK cascade in maintaining synchronized spontaneous Ca2+ oscillations.
Main Methods:
- Cultured hippocampal neurons (1-2 weeks in vitro) were used.
- Calcium imaging with a calcium-sensitive dye assessed spontaneous synaptic activities.
- Neurons were treated with varying concentrations of PD98059 (10, 30, 60 µmol/L) or SB202474 (10, 60 µmol/L) as a control.
Main Results:
- PD98059 at 10 µmol/L had minimal effect on Ca2+ oscillations.
- Higher concentrations (30 and 60 µmol/L) of PD98059 significantly decreased Ca2+ oscillation spike frequency and amplitude.
- The control SB202474 showed no significant inhibition of Ca2+ oscillations.
Conclusions:
- PD98059 inhibits synchronized spontaneous Ca2+ oscillations by blocking MEK.
- The MAPK cascade is necessary for the maintenance of synchronized spontaneous Ca2+ oscillations in hippocampal networks.
