Worldwide, lung cancer is a leading cause of cancer-related death. The most frequent type of lung cancer is non-small cell lung cancer (NSCLC) with an overall 5-year survival rate of less than 20%. This survival rate is even lower, when patients develop distant metastasis. Within the metastatic process is the ability of cells to migrate of high importance. It is knownn that Ca²⁺-activated K⁺ channels (K_Ca3.1) are involved in cell migration, proliferation and cancer progression. Inhibiton of K_Ca3.1, by using its specific blocker TRAM-34 might therefore be a potential option in the treatment of cancer patients. Here, we investigated the role of K_Ca3.1 channels in two strains of the NSCLC cell line A549 with high (A549H) and low (A549L) metastatic potential. Expression analysis of K_Ca3.1 at the mRNA/protein level or with immunofluorescence showed a significantly increased induction of K_Ca3.1 in the A549H cells due to reduced K_Ca3.1 promotor methylation. Patch clamp analysis revealed that the K_Ca3.1-activator 1-ethyl-2-benzimidazolinone (1-EBIO) activated an outward-current with a reversal potential around -82 mV and hyperpolarized the resting membrane potential especially in the A549H cells. These currents were completely suppressed in both cell lines when using TRAM-34 (10 µM) or siRNA against K_Ca3.1. Moreover, blocking K_Ca3.1-channels with TRAM-34 also reduced cell migration and the intracellular Ca²⁺ concentration of the highly metastatic A549H cells, underlining their functional importance.

In conclusion, our results provide evidence that K_Ca3.1 might be involved in the metastatic process of NSCLC.