| First Author | Ransdell JL | Year | 2017 |
| Journal | Cell Rep | Volume | 19 |
| Issue | 3 | Pages | 532-544 |
| PubMed ID | 28423317 | Mgi Jnum | J:250885 |
| Mgi Id | MGI:6103101 | Doi | 10.1016/j.celrep.2017.03.068 |
| Citation | Ransdell JL, et al. (2017) Loss of Navbeta4-Mediated Regulation of Sodium Currents in Adult Purkinje Neurons Disrupts Firing and Impairs Motor Coordination and Balance. Cell Rep 19(3):532-544 |
| abstractText | The resurgent component of voltage-gated Na(+) (Nav) currents, INaR, has been suggested to provide the depolarizing drive for high-frequency firing and to be generated by voltage-dependent Nav channel block (at depolarized potentials) and unblock (at hyperpolarized potentials) by the accessory Navbeta4 subunit. To test these hypotheses, we examined the effects of the targeted deletion of Scn4b (Navbeta4) on INaR and on repetitive firing in cerebellar Purkinje neurons. We show here that Scn4b(-/-) animals have deficits in motor coordination and balance and that firing rates in Scn4b(-/-) Purkinje neurons are markedly attenuated. Acute, in vivo short hairpin RNA (shRNA)-mediated "knockdown" of Navbeta4 in adult Purkinje neurons also reduced spontaneous and evoked firing rates. Dynamic clamp-mediated addition of INaR partially rescued firing in Scn4b(-/-) Purkinje neurons. Voltage-clamp experiments revealed that INaR was reduced (by approximately 50%), but not eliminated, in Scn4b(-/-) Purkinje neurons, revealing that additional mechanisms contribute to generation of INaR. |
