Glutamate-Evoked Ca<sup>2+</sup> Responses in the Rat Suprachiasmatic Nucleus: Involvement of Na<sup>+</sup>/K<sup>+</sup>-ATPase and Na<sup>+</sup>/Ca<sup>2+</sup>-Exchanger
Glutamate mediates photic entrainment of the central clock in the suprachiasmatic nucleus (SCN) by evoking intracellular Ca<sup>2+</sup> signaling mechanisms. However, the detailed mechanisms of glutamate-evoked Ca<sup>2+</sup> signals are not entirely clear. Here, we used a...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6444 |
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| author | Pi-Cheng Cheng Ruo-Ciao Cheng Rong-Chi Huang |
| author_facet | Pi-Cheng Cheng Ruo-Ciao Cheng Rong-Chi Huang |
| author_sort | Pi-Cheng Cheng |
| collection | DOAJ |
| description | Glutamate mediates photic entrainment of the central clock in the suprachiasmatic nucleus (SCN) by evoking intracellular Ca<sup>2+</sup> signaling mechanisms. However, the detailed mechanisms of glutamate-evoked Ca<sup>2+</sup> signals are not entirely clear. Here, we used a ratiometric Ca<sup>2+</sup> and Na<sup>+</sup> imaging technique to investigate glutamate-evoked Ca<sup>2+</sup> responses. The comparison of Ca<sup>2+</sup> responses to glutamate (100 μM) and high (20 mM) K<sup>+</sup> solution indicated slower Ca<sup>2+</sup> clearance, along with rebound Ca<sup>2+</sup> suppression for glutamate-evoked Ca<sup>2+</sup> transients. Increasing the length of exposure time in glutamate, but not in 20 mM K<sup>+</sup>, slowed Ca<sup>2+</sup> clearance and increased rebound Ca<sup>2+</sup> suppression, a result correlated with glutamate-induced Na<sup>+</sup> loads. The rebound Ca<sup>2+</sup> suppression was abolished by ouabain, monensin, Na<sup>+</sup>-free solution, or nimodipine, suggesting an origin of activated Na<sup>+</sup>/K<sup>+</sup>-ATPase (NKA) by glutamate-induced Na<sup>+</sup> loads. Ouabain or Na<sup>+</sup>-free solution also slowed Ca<sup>2+</sup> clearance, apparently by retarding Na<sup>+</sup>/Ca<sup>2+</sup>-exchanger (NCX)-mediated Ca<sup>2+</sup> extrusion. Together, our results indicated the involvement of glutamate-induced Na<sup>+</sup> loads, NKA, and NCX in shaping the Ca<sup>2+</sup> response to glutamate. Nevertheless, in the absence of external Na<sup>+</sup> (NMDG substituted), Ca<sup>2+</sup> clearance was still slower for the Ca<sup>2+</sup> response to glutamate than for 20 mM K<sup>+</sup>, suggesting participation of additional Ca<sup>2+</sup> handlers to the slower Ca<sup>2+</sup> clearance under this condition. |
| first_indexed | 2024-03-11T05:34:36Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:34:36Z |
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| spelling | doaj.art-23047377282e42e0aa1506a9d579a2212023-11-17T16:51:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247644410.3390/ijms24076444Glutamate-Evoked Ca<sup>2+</sup> Responses in the Rat Suprachiasmatic Nucleus: Involvement of Na<sup>+</sup>/K<sup>+</sup>-ATPase and Na<sup>+</sup>/Ca<sup>2+</sup>-ExchangerPi-Cheng Cheng0Ruo-Ciao Cheng1Rong-Chi Huang2Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan 33302, TaiwanDepartment of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan 33302, TaiwanDepartment of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan 33302, TaiwanGlutamate mediates photic entrainment of the central clock in the suprachiasmatic nucleus (SCN) by evoking intracellular Ca<sup>2+</sup> signaling mechanisms. However, the detailed mechanisms of glutamate-evoked Ca<sup>2+</sup> signals are not entirely clear. Here, we used a ratiometric Ca<sup>2+</sup> and Na<sup>+</sup> imaging technique to investigate glutamate-evoked Ca<sup>2+</sup> responses. The comparison of Ca<sup>2+</sup> responses to glutamate (100 μM) and high (20 mM) K<sup>+</sup> solution indicated slower Ca<sup>2+</sup> clearance, along with rebound Ca<sup>2+</sup> suppression for glutamate-evoked Ca<sup>2+</sup> transients. Increasing the length of exposure time in glutamate, but not in 20 mM K<sup>+</sup>, slowed Ca<sup>2+</sup> clearance and increased rebound Ca<sup>2+</sup> suppression, a result correlated with glutamate-induced Na<sup>+</sup> loads. The rebound Ca<sup>2+</sup> suppression was abolished by ouabain, monensin, Na<sup>+</sup>-free solution, or nimodipine, suggesting an origin of activated Na<sup>+</sup>/K<sup>+</sup>-ATPase (NKA) by glutamate-induced Na<sup>+</sup> loads. Ouabain or Na<sup>+</sup>-free solution also slowed Ca<sup>2+</sup> clearance, apparently by retarding Na<sup>+</sup>/Ca<sup>2+</sup>-exchanger (NCX)-mediated Ca<sup>2+</sup> extrusion. Together, our results indicated the involvement of glutamate-induced Na<sup>+</sup> loads, NKA, and NCX in shaping the Ca<sup>2+</sup> response to glutamate. Nevertheless, in the absence of external Na<sup>+</sup> (NMDG substituted), Ca<sup>2+</sup> clearance was still slower for the Ca<sup>2+</sup> response to glutamate than for 20 mM K<sup>+</sup>, suggesting participation of additional Ca<sup>2+</sup> handlers to the slower Ca<sup>2+</sup> clearance under this condition.https://www.mdpi.com/1422-0067/24/7/6444Ca<sup>2+</sup>glutamateNa<sup>+</sup>Na<sup>+</sup>/K<sup>+</sup>-ATPaseNa<sup>+</sup>/Ca<sup>2+</sup> exchangermitochondria |
| spellingShingle | Pi-Cheng Cheng Ruo-Ciao Cheng Rong-Chi Huang Glutamate-Evoked Ca<sup>2+</sup> Responses in the Rat Suprachiasmatic Nucleus: Involvement of Na<sup>+</sup>/K<sup>+</sup>-ATPase and Na<sup>+</sup>/Ca<sup>2+</sup>-Exchanger International Journal of Molecular Sciences Ca<sup>2+</sup> glutamate Na<sup>+</sup> Na<sup>+</sup>/K<sup>+</sup>-ATPase Na<sup>+</sup>/Ca<sup>2+</sup> exchanger mitochondria |
| title | Glutamate-Evoked Ca<sup>2+</sup> Responses in the Rat Suprachiasmatic Nucleus: Involvement of Na<sup>+</sup>/K<sup>+</sup>-ATPase and Na<sup>+</sup>/Ca<sup>2+</sup>-Exchanger |
| title_full | Glutamate-Evoked Ca<sup>2+</sup> Responses in the Rat Suprachiasmatic Nucleus: Involvement of Na<sup>+</sup>/K<sup>+</sup>-ATPase and Na<sup>+</sup>/Ca<sup>2+</sup>-Exchanger |
| title_fullStr | Glutamate-Evoked Ca<sup>2+</sup> Responses in the Rat Suprachiasmatic Nucleus: Involvement of Na<sup>+</sup>/K<sup>+</sup>-ATPase and Na<sup>+</sup>/Ca<sup>2+</sup>-Exchanger |
| title_full_unstemmed | Glutamate-Evoked Ca<sup>2+</sup> Responses in the Rat Suprachiasmatic Nucleus: Involvement of Na<sup>+</sup>/K<sup>+</sup>-ATPase and Na<sup>+</sup>/Ca<sup>2+</sup>-Exchanger |
| title_short | Glutamate-Evoked Ca<sup>2+</sup> Responses in the Rat Suprachiasmatic Nucleus: Involvement of Na<sup>+</sup>/K<sup>+</sup>-ATPase and Na<sup>+</sup>/Ca<sup>2+</sup>-Exchanger |
| title_sort | glutamate evoked ca sup 2 sup responses in the rat suprachiasmatic nucleus involvement of na sup sup k sup sup atpase and na sup sup ca sup 2 sup exchanger |
| topic | Ca<sup>2+</sup> glutamate Na<sup>+</sup> Na<sup>+</sup>/K<sup>+</sup>-ATPase Na<sup>+</sup>/Ca<sup>2+</sup> exchanger mitochondria |
| url | https://www.mdpi.com/1422-0067/24/7/6444 |
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