| First Author | Wu Y | Year | 2023 |
| Journal | Int J Mol Sci | Volume | 24 |
| Issue | 16 | PubMed ID | 37628754 |
| Mgi Jnum | J:339643 | Mgi Id | MGI:7523516 |
| Doi | 10.3390/ijms241612572 | Citation | Wu Y, et al. (2023) CFTR Modulates Hypothalamic Neuron Excitability to Maintain Female Cycle. Int J Mol Sci 24(16) |
| abstractText | Cystic fibrosis transmembrane conductance regulator (CFTR), known as an epithelial Cl(-) channel, is increasingly noted to be expressed in the nervous system, although whether and how it plays a role in neuronal excitability is unclear. Given the association of CFTR with fertility, we tested here possible involvement of CFTR in regulating hypothalamic neuron excitability. Patch-clamp and Ca(2+) imaging showed that pharmacological inhibition of CFTR evoked electrical pulses and Ca(2+) spikes in primary rat hypothalamic neurons, which was dependent on extracellular Cl(-). Hypothalamic neurons in brain-slice preparations from adult female mice with CFTR mutation (DF508) exhibited significantly reduced electrical pulses as compared to the wild-type controls. Removal of extracellular Cl(-) eliminated hypothalamic electrical pulses in the wild-type brain slices, which was reversible by subsequent addition of Cl(-). In adult female mice, Ca(2+) indicator (GCaMP6s)-based fiber-photometry showed that hypothalamic Ca(2+) activities in vivo were enhanced at the proestrus/estrus phase as compared to the diestrus phase of the female cycle. Such estrus-associated hypothalamic activities were largely diminished in DF508 female mice, together with delayed puberty and disturbed female cycles. Therefore, these findings suggest a critical role of CFTR in modulating hypothalamic neuron excitability, which may account for the disturbed female cycles and reduced female fertility associated with CFTR mutations. |
