Publication details

HCN Channel Activity Balances Quiescence and Proliferation in Neural Stem Cells and Is a Selective Target for Neuroprotection During Cancer Treatment

Authors

JOHARD H. OMELYANENKO A. FEI G. ZILBERTER M. DAVE Z. ABU-YOUSSEF R. SCHMIDT L. HARISANKAR A. VINCENT C.T. WALFRIDSSON J. NELANDER S. HARKANY T. BLOMGREN K. ANDÄNG Michael

Year of publication 2020
Type Article in Periodical
Magazine / Source MOLECULAR CANCER RESEARCH
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://mcr.aacrjournals.org/content/18/10/1522
Doi http://dx.doi.org/10.1158/1541-7786.MCR-20-0292
Keywords LONG-TERM; ADULT; NEUROGENESIS; CYCLE; IRRADIATION; RECEPTOR; PURIFICATION; HIPPOCAMPUS; DYNAMICS; CULTURE
Description Children suffering from neurologic cancers undergoing chemotherapy and radiotherapy are at high risk of reduced neurocognitive abilities likely via damage to proliferating neural stem cells (NSC). Therefore, strategies to protect NSCs are needed. We argue that induced cell-cycle arrest/quiescence in NSCs during cancer treatment can represent such a strategy. Here, we show that hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels are dynamically expressed over the cell cycle in NSCs, depolarize the membrane potential, underlie spontaneous calcium oscillations and are required to maintain NSCs in the actively proliferating pool. Hyperpolarizing pharmacologic inhibition of HCN channels during exposure to ionizing radiation protects NSCs cells in neurogenic brain regions of young mice. In contrast, brain tumor-initiating cells, which also express HCN channels, remain proliferative during HCN inhibition.
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