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| Content Provider | PubMed Central |
|---|---|
| Author | Wang, Sho-ya Russell, Corinna Wang, Ging Kuo |
| Copyright Year | 2005 |
| Abstract | Voltage-gated Na+ channels display rapid activation gating (opening) as well as fast and slow inactivation gating (closing) during depolarization. We substituted residue S1759 (serine), a putative D4S6 gating hinge of human cardiac hNav1.5 Na+ channels with A (alanine), D (aspartate), K (lysine), L (leucine), P (proline), and W (tryptophan). Significant shifts in gating parameters for activation and steady-state fast inactivation were observed in A-, D-, K-, and W-substituted mutant Na+ channels. No gating shifts occurred in the L-substituted mutant, whereas the P-substituted mutant did not yield sufficient Na+ currents. Wild-type, A-, D-, and L-substituted mutant Na+ channels showed little or no slow inactivation with a 10-s conditioning pulse ranging from −180 to 0 mV. Unexpectedly, W- and K-substituted mutant Na+ channels displayed profound maximal slow inactivation around −100 mV (∼85% and ∼70%, respectively). However, slow inactivation was progressively reversed in magnitude from −70 to 0 mV. This regression was minimized in inactivation-deficient hNav1.5-S1759W/L409C/A410W Na+ channels, indicating that the intracellular fast-inactivation gate caused such a reversal. Our data suggest that the hNav1.5-S1759 residue plays a critical role in slow inactivation. Possible mechanisms for S1759 involvement in slow inactivation and for antagonism between fast and slow inactivation are discussed. |
| Related Links | http://dx.doi.org/10.1529/biophysj.105.059352 |
| Ending Page | 3999 |
| Page Count | 9 |
| Starting Page | 3991 |
| File Format | |
| ISSN | 00063495 |
| e-ISSN | 15420086 |
| Journal | Biophysical Journal |
| Issue Number | 6 |
| Volume Number | 88 |
| Language | English |
| Publisher | Biophysical Society |
| Publisher Date | 2005-06-01 |
| Access Restriction | Open |
| Rights Holder | Biophysical Society |
| Subject Keyword | Biophysics Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biophysics |
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