Cold exposure causes cell death by depolarization-mediated Ca ²⁺ overload in a chill-susceptible insect

Significance Insects comprise the largest class of animals and include numerous species of direct importance to humans, including pests and pollinators. Cold tolerance is arguably among the most important traits determining the distribution of insects. Hypothermia has been proposed to induce cell injury directly by promoting membrane phase transitions resulting in cell leak. Additionally, hypothermia induces hemolymph hyperkalemia, and it has been proposed that hypothermia induces injury indirectly through the resulting depolarization by inducing Ca 2+ influx promoting apoptosis/necrosis. Here we show that depolarization is a principal mechanism for hypothermic cell injury. Furthermore, we show that intracellular Ca 2+ increases upon depolarization and that this increase must flux through Ca 2+ channels in the membrane to accumulate and induce injury.