Figure 5. N-type (Cav2.2) calcium currents are reduced by CBD3063 in DRG neurons . (A) Summary of bar graph showing the normalized peak ICa2+ density after incubating sensory neurons with DMSO (0.1%), 2, 20 and 50 μM of CBD3063. N=13-30 cells; error bars indicate mean ± SEM; pp value as indicated; Mann-Whitney test. (E) Boltzmann fits for voltage-dependent activation and inactivation kinetics as shown. Half-maximal activation potential of activation and inactivation (V1/2 ) and slope values (k ) for activation and inactivation are presented inTable 2 . N=12-17 cells.
Furthermore, to test any off-target effects of CBD3063 we measured current density–voltage curves and peak current densities for Cav1 (L-type; Figure 6A, B ), Cav2.1 (P/Q-type; Figure 6C, D ), Cav2.3 (R-type; Figure 6E, F ), and Cav3 (T-type; Figure 6G, H ) calcium channels. We found that CBD3063 does not alter Ca2+ influx through these channels when compared to cells treated with 0.1% DMSO. When the voltage-dependence of activation and inactivation of these channels was explored, we observed that CBD3063 did not alter these parameters (Table 2 ). These findings show that CBD3063 selectively modulates the activity of N-type Ca2+channels.