Mode- and cell-type dependent calcium responses induced by electrical stimulus

Intracellular calcium ion concentration ([Ca²⁺]_i) is known to affect numerous molecular signaling events. Regulation of the [Ca²⁺]_i could therefore be used to control important cellular and molecular responses, including cell functionality, survival, differentiation, and proliferation. Because changes in the membrane electrical potential (MEP) activate plasma membrane Ca²⁺ influx pathways and increase the [Ca²⁺]_i level, electrical stimulus (ES) has been used to induce such MEP changes. It now appears that while large ES can directly activate voltage-gated Ca²⁺ channels (VGCCs) by depolarizing the cell membrane, smaller and noninvasive ES could also be applied to activate the Ca²⁺ entry pathways. Elucidation of the electrocoupling mechanisms that control [Ca²⁺]_i increase is complicated by the observations that not only the mode (e.g., dc or oscillatory) of ES application but also the cell type (e.g., excitable or nonexcitable) regulates calcium responses. The aim of this review article is therefore to provide a comparative description for ES mode- and cell type dependent changes in [Ca²⁺]_i.