| First Author | Jin H | Year | 2024 |
| Journal | Mol Brain | Volume | 17 |
| Issue | 1 | Pages | 8 |
| PubMed ID | 38350944 | Mgi Jnum | J:345668 |
| Mgi Id | MGI:7594879 | Doi | 10.1186/s13041-024-01080-y |
| Citation | Jin H, et al. (2024) Deleting IP6K1 stabilizes neuronal sodium-potassium pumps and suppresses excitability. Mol Brain 17(1):8 |
| abstractText | Inositol pyrophosphates are key signaling molecules that regulate diverse neurobiological processes. We previously reported that the inositol pyrophosphate 5-InsP(7), generated by inositol hexakisphosphate kinase 1 (IP6K1), governs the degradation of Na(+)/K(+)-ATPase (NKA) via an autoinhibitory domain of PI3K p85alpha. NKA is required for maintaining electrochemical gradients for proper neuronal firing. Here we characterized the electrophysiology of IP6K1 knockout (KO) neurons to further expand upon the functions of IP6K1-regulated control of NKA stability. We found that IP6K1 KO neurons have a lower frequency of action potentials and a specific deepening of the afterhyperpolarization phase. Our results demonstrate that deleting IP6K1 suppresses neuronal excitability, which is consistent with hyperpolarization due to an enrichment of NKA. Given that impaired NKA function contributes to the pathophysiology of various neurological diseases, including hyperexcitability in epilepsy, our findings may have therapeutic implications. |
