Technical Abstract: Gap junctional intercellular communication (GJIC) is a process whereby cells share molecules and nutrients with each other by physical contact through cell membrane pores. In tumor cells, GJIC is often altered, suggesting that this process may be important in the context of cancer. Certain ion channels, termed KATP channels, are important in maintaining the stability of the cell membrane and have been shown to be closely linked to GJIC; however little is known about the precise mechanistic relationship between GJIC and KATP channels. In this study, we report the effects of the treatment of different cancer cell types with inhibitors of KATP channels. When certain component parts of the KATP channels were inhibited, GJIC increased. These findings highlight novel off-target effects of KATP inhibitors and may be of utility in clinical settings in the future.