Figure 3. The UNC-2(G1132R) corresponding mutation in human CACNA1A, CaV2.1α, subunit results in increased channel activity.

(a) Representative macro-currents of wild type and G1518R CaV2.1 channels. Currents were generated by stepping membrane potential to voltages between −55 and 40 mV in 5 mV increments for 200 ms from a holding potential of −120 mV. (b) Voltage dependence of whole-cell current density for wild type and G1518R CaV2.1 channels. Current density values were obtained by dividing current amplitudes and cell capacitance. (Wild type, n = 13; G1518R, n = 11). (c) Voltage dependence of Ba²⁺ current activation. The activation curve of G1518R exhibits a significant shift of the V_0.5 value towards more negative membrane potentials. (d) Steady-State inactivation curves. The G1518R mutation causes a slight positive shift in the midpoint voltage in the steady-state inactivation curves (V_0.5inact= -55.0 ± 1.0 and −47.3 ± 1.0 for wild type and G1518R, respectively). Currents were normalized to the maximal value obtained at the test pulse and plotted as a function of the prepulse potential. Data were fitted with the Boltzmann equation: (I_max=(1+exp[(V-V0.5)/kin]) - 1). All recordings were carried out in Ba²⁺ solution to exclude the effects from calcium-dependent inactivation.