Fig. 4.

Effect of TNFα pretreatment on H⁺-evoked responses in rat vagal pulmonary sensory neurons. Top: representative experimental records of H⁺ (pH 6.0, 6 s; horizontal bar)-evoked inward currents before and at 0, 30, 60, and 90 min after TNFα (1.44 nM, 9 min) pretreatment in a jugular sensory neuron (24.7 pF). Pretreatment of amiloride (500 µM, 2 min) blocked the transient (ASICs-dependent) current evoked by H⁺ (pH 6.0); after washout of amiloride, pretreatment of AMG9810 (1 µM, 5 min) blocked the sustained (TRPV1-dependent) current evoked by the same acid application. The response to a lower pH (pH 5.5) was tested at both the beginning and the end of experiment to determine if the lack of a potentiating effect on ASICs-dependent currents was due to that the maximal currents were already reached at pH 6.0. Bottom: group data indicating that the H⁺ (pH 6.0)-evoked ASICs-dependent currents were not altered by the TNFα pretreatment (left), whereas TRPV1-dependent currents were clearly potentiated at 0 and 90 min after the TNFα pretreatment (right). C1 and C2: control responses to two consecutive H⁺ challenges separated by 10 min before TNFα. *Significantly different from control. Data are means ± SE (n = 10, except for the data points after amiloride and AMG9810: n = 5 in each).