Deciphering Molecular Mechanisms and Intervening in Physiological and Pathophysiological Processes of Ca(2+) Signaling Mechanisms Using Optogenetic Tools

Calcium ion channels are involved in numerous biological functions such as lymphocyte activation, muscle contraction, neurotransmission, excitation, hormone secretion, gene expression, cell migration, memory, and aging. Therefore, their dysfunction can lead to a wide range of cellular abnormalities and, subsequently, to diseases. To date various conventional techniques have provided valuable insights into the roles of Ca(2+) signaling. However, their limited spatiotemporal resolution and lack of reversibility pose significant obstacles in the detailed understanding of the structure–function relationship of ion channels. These drawbacks could be partially overcome by the use of optogenetics, which allows for the remote and well-defined manipulation of Ca(2+)-signaling. Here, we review the various optogenetic tools that have been used to achieve precise control over different Ca(2+)-permeable ion channels and receptors and associated downstream signaling cascades. We highlight the achievements of optogenetics as well as the still-open questions regarding the resolution of ion channel working mechanisms. In addition, we summarize the successes of optogenetics in manipulating many Ca(2+)-dependent biological processes both in vitro and in vivo. In summary, optogenetics has significantly advanced our understanding of Ca(2+) signaling proteins and the used tools provide an essential basis for potential future therapeutic application.