Fig. 8.
The C121W mutation causes loss of β1-mediated functional modulation of rat Nav1.2a sodium channels expressed in SNaIIA cells. A, Mean current time courses at 0 mV for uninduced SNaIIA-pIND.β1 and SNaIIA-pIND.C121Wβ1 cells, which express rat Nav1.2a alone (solid line,n = 8), and for induced cells expressing Nav1.2a plus β1 (dashed line,n = 6) or Nav1.2a plus C121Wβ1 (dotted line, n = 4). Neither wild-type nor mutant β1 significantly altered current time course.B, Mean V1/2 values for activation (open symbols) and availability (solid symbols) for uninduced SNaIIA cells (SNaIIA-pIND.β1: activation: V1/2 = −16.3 ± 1.1 mV, k = −6.1 ± 0.2; availability: −49.4 ± 1.4, 5.4 ± 0.3, n = 4; SNaIIA-pIND.C121Wβ1: −17.1 ± 1.4, −6.3 ± 0.4, −48.2 ± 2, 5.7 ± 0.4; n = 4) and for induced cells coexpressing β1 (−19 ± 1.4, −6.3 ± 0.3, −59.8 ± 0.8, 5.3 ± 0.2, n = 6) or C121Wβ1 (−18.1 ± 1.5, −6 ± 0.2, −50.1 ± 1.5, 5.6 ± 0.5, n = 4). Induction of wild-type β1 shifted the midpoint of availability significantly negative compared with cells expressing Nav1.2a alone or Nav1.2a with C121Wβ1 (p < 0.001). C, Mean frequency-dependent rundown in uninduced SNaIIA cells (■, n = 8) and in induced cells coexpressing β1 (⋄, n = 6) or C121Wβ1 (▵,n = 4). Wild-type β1 significantly increased frequency-dependent rundown compared with uninduced cells or cells coexpressing C121Wβ1 (p < 0.01).