Spatially Organized β-Cell Subpopulations Control Electrical Dynamics across Islets of Langerhans

Abstract

Understanding how heterogeneous cells within a multicellular system interact and affect overall function is difficult without a means of perturbing individual cells or subpopulations. Here we apply optogenetics to understand how subpopulations of β-cells control the overall [Ca²⁺]_i response and insulin secretion dynamics of the islets of Langerhans. We spatiotemporally perturbed electrical activity in β-cells of channelrhodopsin2-expressing islets, mapped the [Ca²⁺]_i response, and correlated this with the cellular metabolic activity and an in silico electrophysiology model. We discovered organized regions of metabolic activity across the islet, and these affect the way in which β-cells electrically interact. Specific regions acted as pacemakers by initiating calcium wave propagation. Our findings reveal the functional architecture of the islet, and show how distinct subpopulations of cells can disproportionality affect function. These results also suggest ways in which other neuroendocrine systems can be regulated, and demonstrate how optogenetic tools can discern their functional architecture.