{Reference Type}: Journal Article
{Title}: A leak K+ channel TWK-40 sustains the rhythmic motor program.
{Author}: Yue Z;Li Y;Yu B;Xu Y;Chen L;Chitturi J;Meng J;Wang Y;Tian Y;Mouridi SE;Zhang C;Zhen M;Boulin T;Gao S;
{Journal}: PNAS Nexus
{Volume}: 3
{Issue}: 7
{Year}: 2024 Jul
暂无{DOI}: 10.1093/pnasnexus/pgae234
{Abstract}: Leak potassium (K+) currents, conducted by two-pore domain K+ (K2P) channels, are critical for the stabilization of the membrane potential. The effect of K2P channels on motor rhythm remains enigmatic. We show here that the K2P TWK-40 contributes to 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 dorsorectal ganglion ventral process B (DVB), an excitatory GABAergic motor neuron that activates expulsion muscle contraction. In addition, TWK-40 substantially contributes to the rhythmic activity of DVB. Specifically, DVB Ca2+ oscillations exhibit obvious defects in loss-of-function (lf) mutant of twk-40. Expression of TWK-40(gf) in DVB recapitulates the expulsion deficiency of the twk-40(gf) mutant, and inhibits DVB Ca2+ oscillations in both wild-type and twk-40(lf) animals. Moreover, DVB innervated enteric muscles also exhibit rhythmic Ca2+ defects in twk-40 mutants. In summary, these findings establish TWK-40 as a crucial neuronal stabilizer of DMP, linking leak K2P channels with rhythmic motor activity.