| First Author | Hermanstyne TO | Year | 2017 |
| Journal | eNeuro | Volume | 4 |
| Issue | 3 | PubMed ID | 28560311 |
| Mgi Jnum | J:255835 | Mgi Id | MGI:6114520 |
| Doi | 10.1523/ENEURO.0377-16.2017 | Citation | Hermanstyne TO, et al. (2017) Acute Knockdown of Kv4.1 Regulates Repetitive Firing Rates and Clock Gene Expression in the Suprachiasmatic Nucleus and Daily Rhythms in Locomotor Behavior. eNeuro 4(3):ENEURO.0377-16.2017 |
| abstractText | Rapidly activating and inactivating A-type K(+) currents (IA) encoded by Kv4.2 and Kv4.3 pore-forming (alpha) subunits of the Kv4 subfamily are key regulators of neuronal excitability. Previous studies have suggested a role for Kv4.1 alpha-subunits in regulating the firing properties of mouse suprachiasmatic nucleus (SCN) neurons. To test this, we utilized an RNA-interference strategy to knockdown Kv4.1, acutely and selectively, in the SCN. Current-clamp recordings revealed that the in vivo knockdown of Kv4.1 significantly (p < 0.0001) increased mean +/- SEM repetitive firing rates in SCN neurons during the day (6.4 +/- 0.5 Hz) and at night (4.3 +/- 0.6 Hz), compared with nontargeted shRNA-expressing SCN neurons (day: 3.1 +/- 0.5 Hz; night: 1.6 +/- 0.3 Hz). IA was also significantly (p < 0.05) reduced in Kv4.1-targeted shRNA-expressing SCN neurons (day: 80.3 +/- 11.8 pA/pF; night: 55.3 +/- 7.7 pA/pF), compared with nontargeted shRNA-expressing (day: 121.7 +/- 10.2 pA/pF; night: 120.6 +/- 16.5 pA/pF) SCN neurons. The magnitude of the effect of Kv4.1-targeted shRNA expression on firing rates and IA was larger at night. In addition, Kv4.1-targeted shRNA expression significantly (p < 0.001) increased mean +/- SEM nighttime input resistance (Rin; 2256 +/- 166 MOmega), compared to nontargeted shRNA-expressing SCN neurons (1143 +/- 93 MOmega). Additional experiments revealed that acute knockdown of Kv4.1 significantly (p < 0.01) shortened, by approximately 0.5 h, the circadian period of spontaneous electrical activity, clock gene expression and locomotor activity demonstrating a physiological role for Kv4.1-encoded IA channels in regulating circadian rhythms in neuronal excitability and behavior. |
