K _2P channel TWK-40 Regulates a Rhythmic Behavior in C. elegans

Background potassium (K ⁺ ) currents, conducted by two-pore domain K ⁺ (K _2P ) channels, are critical for the stabilization of the membrane potential. The effect of K _2P channels on motor rhythm remains enigmatic. We show here that the K _2P TWK-40 regulates the rhythmic defecation motor program (DMP) in Caenorhabditis elegans . Disrupting TWK-40 suppresses the expulsion defects of nlp-40 and aex-2 mutants. By contrast, a gain-of-function ( gf ) mutant of twk-40 significantly reduces the expulsion frequency per DMP cycle. In situ whole-cell patch clamping demonstrates that TWK-40 forms an outward current that hyperpolarize the resting membrane potential of DVB neuron. In addition, TWK-40 substantially contributes to the rhythmic activity of DVB. Specifically, DVB Ca ²⁺ oscillations exhibit obvious defects in twk-40 mutants. Expression of TWK-40( gf ) in DVB recapitulates the expulsion deficiency of the twk-40(gf) mutant, and inhibits DVB Ca ²⁺ oscillations in both wild-type and twk-40(lf) animals. Moreover, DVB innervated enteric muscles also exhibit rhythmic Ca ²⁺ defects. Taken together, these results demonstrate that TWK-40 is an essential inhibitor of DMP, thus revealing a cellular mechanism linking K _2P channels with rhythmic motor activity.