| First Author | Petrik D | Year | 2011 |
| Journal | Eur J Neurosci | Volume | 34 |
| Issue | 5 | Pages | 695-704 |
| PubMed ID | 21848922 | Mgi Jnum | J:177931 |
| Mgi Id | MGI:5296708 | Doi | 10.1111/j.1460-9568.2011.07799.x |
| Citation | Petrik D, et al. (2011) Modulation by the BK accessory beta4 subunit of phosphorylation-dependent changes in excitability of dentate gyrus granule neurons. Eur J Neurosci 34(5):695-704 |
| abstractText | Large-conductance voltage- and calcium-activated potassium (BK) channels are large-conductance calcium- and voltage-activated potassium channels critical for neuronal excitability. Some neurons express so called fast-gated, type I BK channels. Other neurons express BK channels assembled with the accessory beta4 subunit conferring slow gating of type II BK channels. However, it is not clear how protein phosphorylation modulates these two distinct BK channel types. Using beta4-knockout mice, we compared fast- or slow-gated BK channels in response to changes in phosphorylation status of hippocampus dentate gyrus granule neurons. We utilized the selective PP2A/PP4 phosphatase inhibitor Fostriecin to study changes in action potential shape and firing properties of the neurons. In beta4-knockout neurons, Fostriecin increases BK current, speeds up BK channel activation and reduces action potential amplitudes. Fostriecin increases spiking during early components of an action potential train. In contrast, inhibition of BK channels through beta4 in wild-type neurons or by the BK channel inhibitor Paxilline opposes Fostriecin effects. Voltage clamp recordings of neurons reveal that Fostriecin increases both calcium and BK currents. However, Fostriecin does not activate BK alpha channels in transfected HEK293 cells lacking calcium channels. In summary, these results suggest that fast-gating, type I BK channels lacking beta4 can increase neuronal excitability in response to reduced phosphatase activity and activation of calcium channels. By opposing BK channel activation, the beta4 subunit plays an important role in moderating firing frequency regardless of changes in phosphorylation status. |
