Figure 6.
Integrated ICa during and after a simulated SN DA neuron three spike burst (2 mm Ca2+) measured for hCav1.2 (blue), hCav1.3S (gray), and hCav1.3L (black). A, Cells were stimulated using a modeled 2.4 Hz pacemaker protocol. After ICa stabilization, regular pacemaking was followed by a three spike burst followed by a 1.5-s-long AHP (maximum, −82 mV). The last five APs preceding the burst (baseline) are shown. Representative ICa traces are given for each construct. Right, One single AP command voltage and IISI responses for all three LTCCs (outward signal and IAP were cutoff; again only the Cav1.3 constructs conducted IISI). B, C, The integrated ICa during a single AP (obtained as the mean of the five preceding APs) before the burst was set to 100% and compared with ICa during the three spike burst integrated over the time period equivalent to one AP (B) or the integrated ICa of the first or second AP after the AHP (C). Parameters are given as the median (10th to 90th percentile; outliers illustrated as points). The statistical significance between LTCC constructs was determined using one-way ANOVA (first AP, p < 0.0001; second AP, p = 0.0189; whole burst, p < 0.0001) with Bonferroni post hoc test: ***p < 0.001; **p < 0.01; *p < 0.05. Although the IAP amplitude of the first and second postburst AP was increased for all three LTCC constructs (data not shown), total Ca2+ influx (integrated ICa) was only significantly increased for Cav1.3 constructs (first AP: hCav1.3S, p = 0.0006; hCav1.3L, p = 0.0007; second AP: hCav1.3S, p = 0.0020; hCav1.3L, p = 0.0126; paired Student's t test). Integrated ICa through all three LTCCs was significantly higher during the burst (hCav1.3S, p < 0.0001; hCav1.3L, p = 0.0003; hCav1.2, p < 0.0001; paired Student's t test).