Abstract
The striatum plays an important role in linking cortical activity to basal ganglia output. Striatal neurons exhibit spontaneous slow Ca2+ oscillations that result from Ca2+ release from the endoplasmic reticulum (ER) induced by the mGluR5-IP3R signaling cascade. The maximum duration of a single oscillatory event is about 300 s. A major question arises as to how such a long-duration Ca2+ elevation is maintained. Store-operated calcium channels (SOCCs) are one of the calcium (Ca2+)-permeable ion channels. SOCCs are opened by activating the metabotropic glutamate receptor type 5 and inositol 1,4,5-trisphosphate receptor (mGluR5-IP3R) signal transduction cascade and are related to the pathophysiology of several neurological disorders. However, the functions of SOCCs in striatal neurons remain unclear. Here, we show that SOCCs exert a functional role in striatal GABAergic neurons. Depletion of calcium stores from the ER induced large, sustained calcium entry that was blocked by SKF96365, an inhibitor of SOCCs. Moreover, the application of SKF96365 greatly reduced the frequency of slow Ca2+ oscillations. The present results indicate that SOCCs contribute to Ca2+ signaling in striatal GABAergic neurons, including medium spiny projection neurons (MSNs) and GABAergic interneurons, through elevated Ca2+ due to spontaneous slow Ca2+ oscillations.
Highlights
The calcium ion (Ca2+) is an important messenger for signal transduction, and intracellular Ca2+ concentration ([Ca2+]i) changes in response to various physiological stimuli in both excitable and non-excitable cells (Pasti et al, 1997; Smetters et al, 1999; Berridge et al, 2000)
To elucidate whether Store-operated calcium channels (SOCCs) are present in striatal GABAergic neurons, we performed fluorescence imaging with Fura-2 LR in acute slice preparations obtained from GAD67-GFP knock-in mice in which GFP was expressed in GABAergic neurons (Figure 1A)
The peak amplitudes of [Ca2+]i elevation without and with SKF96365 were 0.0096 ± 0.0003 (n = 197 cells, three slices, three mice) and 0.0042 ± 0.0002 (n = 230 cells, three slices, two mice; p < 0.0001), respectively. These results indicate that SOCCs exist in striatal GABAergic neurons and exert some functional role
Summary
The calcium ion (Ca2+) is an important messenger for signal transduction, and intracellular Ca2+ concentration ([Ca2+]i) changes in response to various physiological stimuli in both excitable and non-excitable cells (Pasti et al, 1997; Smetters et al, 1999; Berridge et al, 2000). We previously reported long-lasting spontaneous intracellular Ca2+ oscillations in rodent striatal neurons (Osanai et al, 2006; Tamura et al, 2014), which lasted as long as 300 s. These slow Ca2+ oscillations were not induced by action potentials, but by Ca2+ release from the ER. Both the metabotropic glutamate receptor type 5 and inositol 1,4,5-trisphosphate receptor (mGluR5-IP3R) signal transduction cascade were involved in these slow Ca2+ oscillations (Tamura et al, 2014), an important issue arises as to how such a long elevation in Ca2+ is maintained
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
