TWIK-related acid sensitive K⁺ (TASK) channels belong to the K2P channel family and contribute significantly to the background conductance in various cell types, e.g. to I_K,SO in cerebellar granule cells. It is known that stimulation of G_q-protein coupled receptors (G_qPCRs) leads to strong and reversible inhibition of TASK channels. Yet the signaling cascade responsible for TASK current suppression is still controversial: Although it was recently suggested that the Ga_q-protein directly inhibits TASK channels via molecular interaction¹, it has been shown before that phospholipase C (PLC) activation is a necessary step in G_qPCR-mediated TASK inhibition². PLC mediates the hydrolysis of Phosphoinositide-4,5-bisphosphate (PI(4,5)P₂), thereby producing the second messengers Diacylglycerol (DAG) and Inositol-1,4,5-trisphosphate (IP₃). We have shown recently by means of switchable phosphatases, that PIP₂ depletion does not account for the TASK channel inhibition³. Here, we examine the role of downstream second messengers produced by PLC.

We investigated the role of DAG in TASK-current modulation in patch clamp experiments by overexpression and pharmacological intervention of DAG metabolizing enzymes. Efficient manipulation of DAG metabolism was evaluated with the fluorescently-tagged DAG sensor PKCg-C1. We find that accelerated DAG clearance leads to faster and more pronounced TASK current recovery after G_qPCR stimulation. These preliminary results are consistent with the role of DAG in the signaling cascade that controls TASK channel inhibition. However, the possible involvement of other second messengers for TASK current suppression requires further investigation.

Supported by DFG grant OL 240/3-1 (FOR 1086) to DO.

1. Chen, X. et al., 2006,PNAS103, 3422–7.

2. Chemin, J. et al., 2003,EMBO J.22, 5403–11.

3. Lindner, M. et al., 2011,J. Physiol.589, 3149–62.