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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/7/6444 |
| Summary: | 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. |
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| ISSN: | 1661-6596 1422-0067 |