We studied the role of tandem pore potassium channels (2PK) on neuronal excitability and synaptic efficacy in the pathway of the acoustic startle response (ASR). Giant neurons in the pontine reticular formation (PnC) play a central role in the ASR pathway because they integrate auditory and modulatory inputs and innervate spinal motoneurons. In-situ hybridizations indicate that acidsensitive TASK-3, but not TASK-1, channels are strongly expressed in PnC giant neurons and their auditory afferents. Using patch-clamp measurements in rat brain slices we observed that acidification to pH 6.4 significantly reduced the whole-cell potassium conductance to 90% (p=0.02; n=10) and depolarized the resting potential from -54.6 mV to -49.7 mV (p=0.001; n=10). Inversely, alkalinization to pH 8.4 increased potassium conductance to 133.2% (p=0.02; n=8) and hyperpolarized the cells by -4.1 mV (p=0.05; n=6). These effects were independent of the "classical" potassium channel blockers TEA and 4-AP. Ruthenium red (RR), a TASK-3 antagonist, but not anandamide, a TASK-1 antagonist, reduced potassium conductance. Stimulation of auditory afferents at pH 6.4 and with RR revealed an EPSC reduction to 71.7% and 46.2% (p=0.02, n=8 and p=0.09, n=6; respectively). Alkalinization potentiated EPSCs to 238.3%. Together these data suggest that TASK-3 channels influence the excitability and synaptic efficacy of PnC giant neurons in the ASR pathway.