Fig. 5: (−)-Englerin A and riluzole binding sites of TRPC5.

a A representative current trace of TRPC5 at − 60 mV upon 20 μM riluzole (beige), 30 nM (−)-Englerin A (EA, pink), and both agonists (green), with I–V relationships from peak points indicated by triangles shown as an inset. b Statistical data of current responses at − 60 mV induced by each agonist combination (n = 11, riluzole; n = 7, EA; n = 7, riluzole + EA). c Summary of dose-dependent responses of TRPC channels with WT or mutant TRPC1/C5 subunits (n = 4–9 for each EA concentration condition, currents obtained at − 60 mV. Detailed data are available in the Source Data file). d Cryo-EM map of TRPC5 homomer (Class 1) in complex with EA and riluzole. The agonist binding regions are highlighted. e–g Close-up view of the interprotomer cavity of the EA-bound TRPC5 (e), apo TRPC5 (f), or TRPC1/C5 heteromer (g). F520 (TRPC5) or F540 (TRPC1) is indicated by the dotted circle. h Close-up view of the VSLD of riluzole-bound TRPC5 (left) and TRPC1 subunit in TRPC1/C5 heteromer (right). i Pore radius calculation using HOLE⁵⁵ to compare the effect of agonists binding to TRPC5. j Sequence alignment of the interprotomer site-forming region of human TRPC1–7. n represents a number of independent cells. Comparisons between groups were conducted using two-sided Student’s t test. Bars represent the mean ± s.e.m. **p  <  0.01.