A locally-induced increase in intracellular Ca²⁺ propagates cell-to-cell in the presence of plasma membrane Ca²⁺ ATPase inhibitors in non-excitable cells

Abstract 

Intercellular Ca²⁺ waves are commonly observed in many cell types. In non-excitable cells, intercellular Ca²⁺ waves are mediated by gap junctional diffusion of a Ca²⁺ mobilizing messenger such as IP₃. Since Ca²⁺ is heavily buffered in the cytosolic environment, it has been hypothesized that the contribution of the diffusion of Ca²⁺ to intercellular Ca²⁺ waves is limited. Here, we report that in the presence of plasma membrane Ca²⁺ ATPase inhibitors, locally-released Ca²⁺ from the flash-photolysis of caged-Ca²⁺ appeared to induce further Ca²⁺ release and were propagated from one cell to another, indicating that Ca²⁺ was self-amplified to mediate intercellular Ca²⁺ waves. Our findings support the notion that non-excitable cells can establish a highly excitable medium to communicate local responses with distant cells.

Abbreviations: PMCA, plasma membrane Ca²⁺ ATPase, CICR, calcium-induced calcium release, Cx43, connexin 43, [Ca²⁺]_i, cytosolic calcium concentration

Keywords: Ca²⁺ signaling, Calcium-induced calcium release, Non-excitable cell, computational model