TY - JOUR AU - Rui Yan-fang AU - Sun Zhao-hui AU - Gu Jia-ping AU - Sheng Zhong-hua AU - He Xiang-ping AU - Xie Zuo-ping PY - 2016 TI - MEK inhibitor PD98059 acutely inhibits synchronized spontaneous Ca2+ oscillations in cultured hippocampal networks JF - Acta Pharmacologica Sinica; Vol 27, No 7 (July 2006): Acta Pharmacologica Sinica(Special Issue on Calcium signaling) Y2 - 2016 KW - N2 - Aim: To investigate the changes in synchronized spontaneous Ca 2+ 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 Ca 2+ imaging using calcium-sensitive dye. MEK inhibitor PD98059 (10, 30, and 60 μmol/L) and SB202474 (10 and 60 μmol/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 μmol/L had little effect on the Ca 2+ oscillation. At the higher concentration of 30 μmol/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 μmol/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 μmol/L had little inhibition effect on the Ca 2+ oscillation. Conclusion: These results indicate that PD98059 inhibits synchronized spontaneous Ca 2+ oscillation through inhibition of MEK, which hints that the MAPK cascade is required to maintain synchronized spontaneous Ca 2+ oscillation. UR - http://www.chinaphar.com/article/view/4013