Table 2.
Main Electrophysiological Parameters of IIS6 and IIS4-S5 Variants Causing Gain-of-Function
|
Current Density |
Steady-State Activation |
Inactivation |
||
|---|---|---|---|---|
| (pA/pF) | V1/2 (mV) | kV (mV) | r400 at +5 mV | |
| IIS6 Variants in α1E-1+ β2d; 15 mM Ba2+ | ||||
| Wild-type | −183.1 ± 17.7 (24) | −9.7 ± 0.8 (24) | 5.0 ± 1.1 (24) | 0.27 ± 0.09 (24) |
| p.Phe698Ser | −121.4 ± 17.1 (11) | −20.1 ± 1.2 (11)∗∗∗ | 5.1 ± 0.7 (11) | 0.53 ± 0.05 (11)∗∗ |
| p.Ile701Val | −186.9 ± 27.8 (10) | −20.5 ± 1.2 (10)∗∗∗ | 4.3 ± 0.7 (10) | 0.40 ± 0.04 (10)∗ |
| p.Ala702Thr | −184.5 ± 34.2 (9) | −20.4 ± 1.4 (9)∗∗∗ | 4.2 ± 0.3 (9) | 0.45 ± 0.05 (9)∗∗ |
| IIS4-S5 Linker Variant α1E-3+ β1b+α2δ; 2 mM Ca2+ | τinact (ms) at +5 mV | |||
| Wild-type | −47.8 ± 10.9 (13) | −18.0 ± 1.6 (13) | 4.4 ± 0.5 (13) | 66.1 ± 8.9 (9) |
| p.Ile603Leu | −192.3 ± 20.4 (16)∗∗∗∗ | −29.4 ± 2.7 (10)∗∗ | 3.1 ± 0.3 (10) | 80.6 ± 8.7 (10) |
| IIS4-S5 Linker Variant α1E-3+ β1b+α2δ; 5 mM Ba2+ | τinact (ms) at +5 mV | |||
| Wild-type | −105.9 ± 18.3 (13) | −18.8 ± 1.5 (10) | 4.7 ± 0.2 (10) | 58.6 ± 3.6 (7) |
| p.Ile603Leu | −197.5 ± 35.2 (13)∗ | −31.9 ± 2.1 (10)∗∗∗∗ | 3.7 ± 0.6 (10) | 109.9 ± 13.9 (8)∗∗ |
V1/2 is the voltage of half-maximal activation, kV is a slope factor, r400 is the residual current in a 400-ms lasting pulse to 5 mV normalized to the peak current of the same trace, τinact is the exponential time constant of inactivation; numbers in brackets indicate the number of cells that were analyzed for this parameter, data are represented as mean ± SEM; ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001.