Fig. 4

ANO1 modulation of capsaicin triggered action potentials in DRG neurons is determined by [Cl⁻]_i. a The average number of action potentials (APs) by DRG neurons over 25 s increased by perfusion of TRPV1-activator capsaicin (15 µM, Cap, red bars) from baseline (Pre, black bars) were significantly lowered by perfusion of an ANO1-inhibitor 20 µM T16A[inh]-A01 mixed with capsaicin (Cap&ANO1-inh, blue bars) when the intracellular solutions contained concentrations of: 160 mM Cl⁻ (High [Cl⁻]_i, n = 5) or 40 mM Cl⁻ (Mid [Cl⁻]_i, n = 3). b APs recorded in representative DRG neurons with intracellular solutions of High [Cl⁻]_i (upper graph) or Mid [Cl⁻]_i (lower graph) at baseline (black traces) and following perfusions of 15 µM capsaicin (red traces) and 20 µM ANO1-inh/15 µM capsaicin mixture (blue traces). c In DRG neurons with intracellular solutions containing 10 mM Cl⁻ (Low [Cl⁻]_i, n = 4), the increased average number of action potentials over 25 s by capsaicin (15 µM, white bars) perfusion from baseline (black bars) were significantly lowered by perfusion of an N-aroylaminothiazole ANO1-activator (E-act, 10 µM) mixed with 15 µM capsaicin (green bars). Perfusion of 20 µM ANO1-inh mixed with 15 µM capsaicin (blue bars) restored the action potential firing to the level of capsaicin alone. d APs recorded in a representative DRG neuron with intracellular solution of Low [Cl⁻]_i at baseline (black traces) and bath perfusions of 15 µM capsaicin (red traces), 10 µM E-act with capsaicin mixture (green traces) and 20 µM ANO1-inh with capsaicin (blue traces). Error bars are SE. (**p > 0.01). DRG neurons were recorded in perforated-patch current clamp with a similar current injection protocol as Fig. 2a