Figure 4. CB1 activation can inhibit TRPM3 channels.
(a) Effect of CB1 receptor agonist WIN 55212–2 (1 µM) on DRG [Ca2+]i-responses evoked by PS (20 µM, second application). ***p<0.001; Mann-Whitney U test (control, n = 213; WIN 55212–2, n = 218). (b) Traces showing DRG [Ca2+]i responses to three PS (20 µM) challenges in the absence and presence of WIN 55212–2 (1 µM) and WIN 55212–2 (1 µM) plus AM251 (0.5 µM) followed by high K+ (50 mM KCl). Many PS responses were unaffected by WIN 55212–2 (upper panel) and some showed an inhibition that was reversed by co-application of the antagonist AM251 with WIN 55212–2 (bottom panel). (c) Traces displaying [Ca2+]i responses to sequential 20 µM PS challenges (indicated by black bars) in CHO cells co-expressing TRPM3 and CB1 receptors in the absence (top) and presence (middle) of 1 µM WIN 552212–2 during the second PS challenge. Middle traces show cells where WIN 552212–2 inhibited the PS responses. Bottom: [Ca2+]i responses to sequential applications of 5 µM PS with 0.5 µM present during the second PS application. (d) Plots showing the change in [Ca2+]i response amplitudes (second – first response). Note the increased number of negative values (inhibition) and the increased number of positive values (potentiation) in the presence of the agonist WIN 552212–2 and antagonist AM251, respectively.