The KCNK3 Knockout PaTu 8988t Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal population of human PaTu 8988t pancreatic adenocarcinoma cells in which the KCNK3 gene has been disrupted, resulting in loss of the encoded TASK-1 potassium channel. This loss-of-function model enables systematic investigation of background potassium currents in cellular excitability, pH-sensing, and oxygen-sensing pathways. The polyclonal format retains the genetic diversity of the edited pool, reducing clonal selection artifacts, while the CRISPR/Cas9-mediated gene disruption ensures stable and heritable silencing of the target locus.
The host cell line PaTu 8988t, derived from a liver metastasis of a human pancreatic ductal adenocarcinoma, displays adherent epithelial morphology and is widely employed as a model for metastatic pancreatic cancer. It recapitulates key features of advanced disease, including invasive growth, altered metabolism, and therapeutic resistance. This cell line is particularly suited for dissecting molecular mechanisms underlying tumor progression and the metastatic niche.
KCNK3 encodes TASK-1 (TWIK-related acid-sensitive K+ channel 1), a two-pore domain potassium channel mediating pH-sensitive background potassium currents that set the resting membrane potential. TASK-1 is inhibited by extracellular acidosis, hypoxia via HIF-1??, and GPCR signals such as AT1R activation, as well as by PKA, PKC, and volatile anesthetics. It interacts with regulatory proteins including 14-3-3 scaffolds, SUMO, syntaxin-1A, endophilin-1, and microtubule-associated protein 1B (MAP1B). Downstream, TASK-1 loss disrupts calcium signaling, cell proliferation, apoptosis, and aldosterone secretion. KCNK3 thus integrates environmental and intracellular cues to control cellular electrical state and effector pathways.
In pancreatic adenocarcinoma, the acidic and hypoxic microenvironment likely suppresses TASK-1; KCNK3 knockout in PaTu 8988t cells allows dissection of how pH- and oxygen-sensing pathways govern viability, migration, and invasion??processes critical for metastasis. Additionally, since KCNK3 dysfunction is associated with pulmonary arterial hypertension, cardiac arrhythmia, and aldosterone-producing adenomas, this model enables cross-disease comparisons of potassium channel pathology.
This knockout cell population is optimized for electrophysiological characterization using patch-clamp recording, and molecular analyses such as western blotting, RT-qPCR, and immunofluorescence to verify KCNK3 ablation and localization. Functional assays including MTT-based viability, transwell migration/invasion, calcium imaging, and potentiometric dye-based membrane potential measurements are directly applicable. The product supports research into ion channel pharmacology, hypoxic signaling, and pancreatic cancer progression. For further information, please contact Ascent Research.
