科研之友
微信
新浪微博
Facebook
分享链接
摘要
The importance of Ca2+ signaling in astrocytes is undisputed but a potential role of Ca2+ influx via L-channels in the brain in vivo is disputed, although expression of these channels in cultured astrocytes is recognized. This study shows that an increase in free cytosolic Ca2+ concentration ([Ca2+](i)) in astrocytes in primary cultures in response to an increased extracellular K+ concentration (45 mM) is inhibited not only by nifedipine (confirming previous observations) but also to a very large extent by ryanodine, inhibiting ryanodine receptor-mediated release of Ca2+, known to occur in response to an elevation in [Ca2+](i). This means that the actual influx of Ca2+ is modest, which may contribute to the difficulty in demonstrating L-channel-mediated Ca2+ currents in astrocytes in intact brain tissue. Chronic treatment with any of the 3 conventional anti-bipolar drugs lithium, carbamazepine or valproic acid similarly causes a pronounced inhibition of K+-mediated increase in [Ca2+](i). This is shown to be due to an inhibition of capacitative Ca2+ influx, reflected by decreased mRNA and protein expression of the 'transient receptor potential channel' (TRPC1), a constituent of store-operated channels (SOCEs). Literature data are cited (i) showing that depolarization-mediated Ca2+ influx in response to an elevated extracellular K+ concentration is important for generation of Ca2+ oscillations and for the stimulatory effect of elevated K+ concentrations in intact, non-cultured brain tissue, and (ii) that Ca2+ channel activity is dependent upon availability of metabolic substrates, including glycogen. Finally, expression of mRNA for Ca(v)1.3 is demonstrated in freshly separated astrocytes from normal brain.
- 出版日期2013-11
- 单位中国医科大学
