Fig. 2.

Modulation of Ca_V1.2 gating by S4 charge neutralisations. Activation (a) and deactivation (b, tail current) of I _Ba through wild-type and mutant channel constructs with partially neutralised S4 segments (IS4_N+R276, IIS_4N+R662, IIIS4_{N+R1041+R1037}). The deactivation was measured by applying the voltage steps to different potentials after a short (20 ms) activating pulse (b). Note that neutralisation of S4 charges has minor effects on activation and deactivation kinetics of Ca_V1.2. c–f Averaged activation curves of wild-type, IS4_N+R276, IS4_N+R276+R273, IIS_4N+R662, IIS_4N+R662+R652, IIIS4_{N+R1041+R1037} and R1359Q channel constructs. The slope of IS4_N+R267 (c) and IIIS4_{N+R1041+R1037} (e) activation curves was significantly reduced (k _act = 5.9 ± 0.9 mV in WT vs 8.5 ± 0.6 mV and 9.9 ± 0.7 mV in IS4_N+R267 and IIIS4_{N+R1041+R1037} respectively)