Integrating Bioelectrical Currents and Ca²⁺ Signaling with Biochemical Signaling in Development and Pathogenesis

Roles of bioelectrical signals are increasingly recognized in excitable and nonexcitable non-neural tissues. Diverse ion-selective channels, pumps, and gap junctions participate in bioelectrical signaling, including those transporting calcium ions (Ca²⁺). Ca²⁺ is the most versatile transported ion, because it serves as an electrical charge carrier and a biochemical regulator for multiple molecular binding, enzyme, and transcription activities. We aspire to learn how bioelectrical signals crosstalk to biochemical/biomechanical signals. In this study, we review four recent studies showing how bioelectrical currents and Ca²⁺ signaling affect collective dermal cell migration during feather bud elongation, affect chondrogenic differentiation in limb development, couple with mechanical tension in aligning gut smooth muscle, and affect mitochondrial function and skeletal muscle atrophy. We observe bioelectrical signals involved in several developmental and pathological conditions in chickens and mice at multiple spatial scales: cellular, cellular collective, and subcellular. These examples inspire novel concept and approaches for future basic and translational studies.