Dorsal vagal neurons (DVN) receive serotonergic inputs from higher CNS centres (e.g. medullary raphé nuclei) suggesting that 5-HT may exert fine modulation of vagal activity. Previous studies have shown that 5-HT increases DVN excitability in part by inhibition of a K⁺ current via postsynaptic activation of 5-HT_2A receptors [1,2]. As mRNA for the two-pore-domain K⁺ channels TASK and TREK has been found in DVN [3] we investigated a possible contribution of these channels to the 5-HT-inhibited K⁺ conductance using whole-cell patch-clamp techniques. Brainstem slices (200 μm) were obtained from 8-25 day-old Sprague-Dawley rats after anaesthesia (halothane). Following recovery at 34°C for 60 min, slices were maintained in ACSF (in mM: 3 KCl, 118 NaCl, 25 NaHCO₃, 1.2 NaH₂PO₄, 1 MgCl₂, 1.5 CaCl₂, 10 glucose; pH 7.4) at RT. Recordings from DVN were established using borosilicate glass electrodes (3-6 MΩ) filled with (in mM): 120 K-gluconate, 1 NaOH, 1 MgCl₂, 1 CaCl₂, 10 HEPES, 5 BAPTA, 2 K₂ATP, pH 7.3. Membrane properties were monitored with repetitive 1 s voltage ramps from a holding potential of -20 mV to -120 mV. All values are given as mean ± s.e.m. In current clamp in ACSF, 5-HT (20 μM) elicited a depolarisation by 5.1 ± 1.5 mV (n=7) and an increase in firing rate. In voltage clamp, 5-HT (20 μM) reduced the standing outward current (I_SO) at -20 mV by 65 ± 12 pA (n=9), inhibiting a conductance (reversal: -95 ± 4 mV, n=8) which displayed Goldman-Hodgkin-Katz outward rectification, supportive of a TASK-like K⁺ current. Since TASK channels are modulated by extracellular pH, we investigated the pH-sensitivity of I_SO in DVN. Voltage clamp recordings were performed in HEPES-buffered ACSF (in mM: 3 KCl, 118 NaCl, 1 MgCl₂, 1.5 CaCl₂, 25 HEPES, 10 glucose; pH adjusted with NaOH). At pH 7.3, DVN exhibited an I_SO of 144 ± 22 pA (n=14) at -20 mV. Acidification of the ACSF to pH 6.3 reduced I_SO to 86 ± 14 pA (n=13), whereas raising extracellular pH to 8.5 increased I_SO to 219 ± 31 pA (n=15). At pH 8.5, BaCl₂ (1 mM) inhibited I_SO by 115 ± 37 pA (n=6). I_SO was unaffected by ZnCl₂ (100 μM) at pH 7.3 (n=4). 5-HT (10 μM) reduced I_SO by 122 ± 18 pA (n=5) at pH 7.3, whereas at pH 6.3 the 5-HT-induced inhibition of I_SO was 74 ± 7% (n=5) smaller. The present data show that the excitatory effects of 5-HT on DVN may be mediated in part by inhibition of a TASK-like, pH-sensitive K⁺ conductance. The pharmacological profile of I_SO suggests that TASK-1 (rather than TASK-3 or TREK) current is inhibited by 5-HT.