Channel | Control | Control | R(+)-Bupivacaine | S(−)-Bupivacaine | ||||
---|---|---|---|---|---|---|---|---|
V0.5 | k | S′0.5 | kS′ | S′0.5 | kS′ | S′0.5 | kS′ | |
mV | ||||||||
Wild-type | −82.1 ± 1.4 | 5.4 ± 0.1 | −63.0 ± 2.5 | 12.7 ± 1.1 | −102.3 ± 0.5 | 7.6 ± 0.4 | −102.5 ± 0.6 | 7.9 ± 0.5 |
(n = 10) | (n = 22) | (n = 11) | (n = 11) | |||||
N434A | −69.5 ± 1.4 | 6.8 ± 0.4 | −71.4 ± 0.1 | 5.5 ± 0.9 | −97.9 ± 1.9 | 5.3 ± 1.7 | −94.9 ± 1.6 | 4.9 ± 1.3 |
(n = 4) | (n = 21) | (n = 10) | (n = 11) | |||||
N434F | −96.3 ± 1.8 | 6.3 ± 0.2 | −82.2 ± 0.7 | 11.7 ± 0.6 | −111.5 ± 2.7 | 6.8 ± 2.4 | −113.8 ± 4.3 | 7.1 ± 3.7 |
(n = 11) | (n = 17) | (n = 4) | (n = 4) | |||||
N434W | −98.2 ± 0.4 | 7.4 ± 0.3 | −74.4 ± 2.0 | 16.0 ± 1.2 | −115.7 ± 1.6 | 9.2 ± 1.5 | −115.5 ± 2.6 | 7.1 ± 2.3 |
(n = 5) | (n = 9) | (n = 5) | (n = 4) | |||||
N434Y | −114.2 ± 2.7 | 8.6 ± 0.1 | −36.6 ± 30.6 | 36.8 ± 8.7 | −133.5 ± 3.4 | 9.1 ± 2.7 | −139.0 ± 5.3 | 9.3 ± 3.7 |
(n = 7) | (n = 8) | (n = 4) | (n = 4) | |||||
N434T | −78.9 ± 1.2 | 7.3 ± 0.2 | −65.2 ± 0.3 | 6.2 ± 0.2 | −105.5 ± 2.3 | 8.5 ± 2.1 | −99.5 ± 1.9 | 7.8°1.7 |
(n = 7) | (n = 11) | (n = 5) | (n = 6) | |||||
N434C | −98.8 ± 1.9 | 6.4 ± 0.2 | −86.9 ± 0.3 | 9.7 ± 0.3 | −124.0 ± 7.5 | 6.8 ± 6.5 | −119.5 ± 5.7 | 4.2 ± 5.8 |
(n = 10) | (n = 25) | (n = 11) | (n = 10) | |||||
N434D | −87.3 ± 0.8 | 5.6 ± 0.4 | −53.3 ± 9.1 | 16.8 ± 2.7 | −110.9 ± 0.8 | 9.2 ± 0.7 | −111.6 ± 0.6 | 8.4 ± 0.5 |
(n = 5) | (n = 20) | (n = 11) | (n = 9) | |||||
N434K | −77.7 ± 1.3 | 7.0 ± 0.4 | −54.0 ± 6.6 | 14.4 ± 2.0 | −88.9 ± 1.1 | 5.9 ± 1.0 | −92.6 ± 1.6 | 7.3 ± 1.4 |
(n = 9) | (n = 15) | (n = 8) | (n = 7) | |||||
N434R | −83.3 ± 0.5 | 6.1 ± 0.1 | −62.6 ± 5.9 | 15.8 ± 2.5 | −97.1 ± 0.6 | 9.6 ± 0.5 | −92.2 ± 0.7 | 9.8 ± 0.6 |
(n = 9) | (n = 16) | (n = 8) | (n = 8) |
The values for the voltage dependence of fast inactivation V0.5and k (mean ± S.E., n = number of experiments) and the slow inactivation S′0.5 and ks′ (fitted values ± S.E.) in the absence and presence of 100 μM (μl wild-type, μl-N434A, μl-N434T, μl-N434D, μl-N434K, μl-N434R) or 10 μM (μl-N434C, μl-N434F, μl-N434Y, μl-N434W) bupivacaine enantiomers were determined as described in Fig. 2.