Temperature-induced modulation of voltage-gated ion channels in human lung cancer cell line A549 using automated patch clamp technology

In cancer cells specific ion channels exhibit altered channel expression, which can drive malignant and metastatic cell behavior. Hence, therapeutic strategies modulating ion channels prove to be promising in cancer therapeutics. Alterations in temperature, even small deviations from normothermia, may cause changes in electrophysiological processes, since activation and conductivity of various ion channels are temperature-dependent. In this pilot study, we focused on a basic understanding of the effects of temperature-alterations on voltage-gated ion channels of A549 cells using an automated patch-clamp system. The measurements were carried out in whole-cell voltage-clamped configuration applying test pulses between −60 and +60 mV. For positive voltages the ion-current curves showed an instantaneously increased conductance, followed by a slow current increase provoked by later activating voltage-gated ion channels, indicating the time-delayed response of additional channels. To investigate the temperature-dependent electrophysiological behavior, six cells (passages 7–10, n = 34) were examined at room temperature and normal body temperature. Compared to normal body temperature, reduced temperatures revealed a higher whole-cell current at negative voltages (63.4% (±18.5%), −60 mV) and lower currents (52.6% (±27.3%), +60 mV) at positive voltages, indicating a hypothermia-induced modulation of voltage-gated channels in the lung cancer cell line A549.