Table 2.
Biophysical parameters of NaV1.4 variants
|
Activation |
Fast inactivation |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| N | IPeak at 0 mV (pA/pF) | N | V1/2(mV) | Vslope(mV) | V1/2(mV) | Vslope(mV) | τInactivation at 0 mV (ms) | N | TRecovery(ms) | ||
| Wild type | 149 | −127·5 (6·4) | 146 | −19·5 (0·2) | 6·4 (0·1) | −65·3 (0·3) | 5·4 (0·0) | 0·30 (0·00) | 105 | 5·63 (0·14) | |
| SIDS cohort | |||||||||||
| Ser682Trp | 19 | −94·2 (9·9) | 17 | −21·2 (0·7) | 7·2 (0·2)* | −67·0 (0·6) | 5·9 (0·2) | 0·40 (0·02)* | 17 | 6·15 (0·33) | |
| Gly859Arg | 18 | −138·5 (16·4) | 17 | −20·2 (0·8) | 5·7 (0·2) | −64·2 (0·6) | 5·1 (0·1) | 0·31 (0·01) | 17 | 5·20 (0·30) | |
| Val1442Met | 14 | −145·5 (21·7) | 14 | −21·7 (0·8) | 6·3 (0·2) | −71·9 (1·0)* | 5·2 (0·1) | 0·27 (0·01) | 13 | 8·51 (0·46)* | |
| Arg1463Ser | 27 | −71·3 (8·3)* | 25 | −17·4 (0·5) | 6·7 (0·2) | −61·7 (0·6)* | 6·3 (0·1)* | 0·31 (0·01) | 19 | 1·95 (0·09)* | |
| Met1493Val | 17 | −78·2 (8·3) | 17 | −19·2 (0·5) | 6·7 (0·3) | −65·3 (0·8) | 5·5 (0·2) | 0·29 (0·01) | 7 | 5·76 (0·47) | |
| Glu1520Lys | 39 | −49·8 (9·7)* | 28 | −20·3 (0·4) | 6·3 (0·1) | −66·3 (0·5) | 5·4 (0·2) | 0·33 (0·01) | 20 | 5·63 (0·29) | |
| Control cohort | |||||||||||
| Arg179Gln | 11 | −117·6 (11·0) | 11 | −19·3 (0·6) | 6·5 (0·2) | −65·1 (0·7) | 5·1 (0·1) | 0·25 (0·01) | 11 | 4·73 (0·30) | |
| Arg190Trp | 14 | −153·4 (21·8) | 14 | −20·7 (0·5) | 6·4 (0·2) | −64·9 (0·5) | 5·3 (0·1) | 0·29 (0·01) | 13 | 5·09 (0·20) | |
| Leu227Phe | 12 | −107·7 (16·1) | 12 | −17·6 (0·4) | 6·5 (0·2) | −67·8 (0·8) | 5·6 (0·1) | 0·33 (0·02) | 10 | 5·33 (0·30) | |
| Asp334Asn | 10 | −141·0 (26·6) | 10 | −21·0 (0·9) | 6·4 (0·2) | −66·4 (0·8) | 5·3 (0·1) | 0·27 (0·01) | 9 | 5·07 (0·30) | |
| Gly863Arg | 12 | −124·6 (15·8) | 12 | −20·3 (0·8) | 6·3 (0·1) | −66·1 (0·7) | 5·2 (0·2) | 0·29 (0·01) | 10 | 5·71 (0·21) | |
| Ala870Thr | 16 | −132·6 (20·0) | 15 | −20·0 (0·6) | 6·4 (0·1) | −65·7 (0·6) | 5·0 (0·1) | 0·29 (0·01) | 14 | 6·29 (0·55) | |
| Met897Lys | 10 | −102·8 (23·3) | 9 | −20·4 (0·7) | 6·8 (0·3) | −67·7 (1·3) | 5·5 (0·2) | 0·31 (0·02) | 7 | 6·21 (0·54) | |
| Val1590Ile | 8 | −92·8 (13·2) | 8 | −20·7 (0·6) | 6·8 (0·2) | −65·8 (0·9) | 5·4 (0·2) | 0·30 (0·02) | 7 | 5·73 (0·61) | |
Data are mean (SE). N indicates the number of cells recorded from. IPeak includes all cells with current amplitude larger than 0·1 nA. Only cells with IPeaklarger than 0·5 nA were included in the analysis of the other biophysical properties. Voltage dependence of activation and fast inactivation, and time constant of open state fast inactivation were all analysed in the same recording for each cell.
p value compared with wild type is less than the Bonferroni threshold (p=0·00051; 98 tests from 14 variants and seven parameters). The appendix shows uncorrected p values (p 6–7). Ipeak=peak current density. V1/2=the voltage of half-maximal activation or inactivation. Vslope=slope factor. τInactivation=time constant of open state fast inactivation. TRecovery=time constant of recovery from inactivation.