The KCNK3 Knockout NCI-H1703 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout population derived from the human non-small cell lung carcinoma line NCI-H1703, with targeted disruption of the KCNK3 gene. KCNK3 encodes the TASK-1 (K2P3.1) two-pore domain potassium channel, which mediates background K+ leak currents essential for setting the resting membrane potential. The polyclonal format consists of a heterogeneous pool of editing events, yielding a versatile loss-of-function model without the need for clonal isolation. This knockout abolishes TASK-1 channel activity, enabling researchers to probe the functional roles of this channel in a lung epithelial carcinoma background.
The parental NCI-H1703 cell line was established from a primary lung squamous cell carcinoma and serves as a widely used model for non-small cell lung cancer (NSCLC). These cells display epithelial morphology and retain characteristic squamous markers, facilitating studies of cancer cell proliferation, migration, and response to microenvironmental stresses such as hypoxia and acidosis. The polyclonal knockout cells maintain the core oncogenic features of the parental line while cleanly eliminating KCNK3 expression, making them ideal for comparative functional analyses.
TASK-1 channels, encoded by KCNK3, are inhibited by hypoxia, acidosis, and Gq-coupled GPCRs (via G??q/11, PLC??, and DAG) and activated by PKA-mediated phosphorylation downstream of cAMP. They form heterodimers with KCNK9 (TASK-3) and interact with partners including 14-3-3 proteins, arrestin beta 1, and G?¦? subunits. Functionally, TASK-1 drives membrane hyperpolarization, which reduces voltage-gated Ca2+ influx and suppresses action potential firing. In this knockout model, elimination of TASK-1 disrupts this signaling axis, causing constitutive membrane depolarization, altered Ca2+ dynamics, and impaired cellular responses to hypoxic and acidotic challenges.
In the NCI-H1703 lung carcinoma context, KCNK3 knockout allows dissection of TASK-1??s contribution to cancer cell excitability, growth, and stress responses. Although best characterized in pulmonary vascular smooth muscle and ventilatory control, TASK-1 may influence tumor cell proliferation, apoptosis, and migration under hypoxia, a common feature of the tumor microenvironment. The polyclonal knockout model enables investigation of how KCNK3 loss modifies sensitivity to hypoxia and acidosis, and provides a platform for pharmacological rescue experiments targeting cAMP/PKA or Gq-coupled pathways.
Typical experimental applications include patch-clamp electrophysiology to confirm loss of TASK-1 currents, Western blotting or RT-qPCR for knockout validation, and functional assays such as MTT/XTT proliferation, Annexin V apoptosis, calcium imaging, and Transwell migration under normoxic or controlled hypoxic conditions. The model is well-suited for drug screening efforts to identify KCNK3 modulators and for studies of pulmonary hypertension and sleep apnea mechanisms, where KCNK3 is genetically implicated. For further information or ordering, please contact Ascent Research.
