Neurons that have AH (designation of neurons with a prominent and prolonged afterhyperpolarizing potential that follows the action potential) electrophysiological characteristics and type 11 morphology (AH/type 11 neurons) are the first neurons in reflex circuits in the small intestine. Thus, the state of excitation of these neurons strongly influences the properties of enteric reflexes. The resting outward current in the type 11 neurons is reduced, causing depolarization and increased excitability, when protein kinase C (PKC) or synaptic inputs are activated, suggesting that regulation of background channels is an important determinant of the state of excitability of these neurons. However, the channels that carry the background current are not yet identified. We used intracellular microelectrodes to record from myenteric AH/type 11 neurons of the guinea-pig ileum, immunohistochemistry to localize channels and reverse transcriptase-polymerase chain reaction (RT-PCR) to characterize channel transcripts. The blockers of TASK1 channels, bupivacaine (1 mM) and methanandamide (10 mu M), depolarized AH/type 11 neurons by 11.6 mV and 7.9 mV, respectively, and increased resting input resistance by about 30%. The reversal potential determined for the effect of bupivacaine was -92 mV, indicating that bupivacaine acts at K+ channels, without significant action on other channel types that are open at rest. The membrane potential of type 11 neurons was depolarized by acidification to pH 6.4, but this depolarization was associated with decreased input resistance and was not reduced by bupivacaine. Thus an unidentified current that is activated by reduced pH masks effects on TASK channels. Slow excitatory post-synaptic potentials in the neurons were reduced in amplitude by methanandamide, suggesting that they are generated in part by closure of TASK1 channels. TASK1 immunoreactivity occurred in all type 11 neurons (determined by double labeling for 1134 and NeuN), but no type 11 neurons were immunoreactive for TASK2 or TASK3. These latter channels were localized to non-type 11 neurons. Transcripts for TASK1, TASK2, TASK3 and other two-pore-domain potassium channels were found in ganglion extracts. It is concluded that TASK1 channels contribute to the resting outward current in AH/type 11 neurons, and that neurotransmitters that evoke slow depolarizations in these neurons do so through the closure of resting K+ channels that include TASK1 channels. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.