An Inconvenient Truth: Calcium Sensors Are Calcium Buffers

• Published in: Trends in neurosciences (Regular ed.) Vol. 41; no. 12; pp. 880 - 884
• Main Authors: McMahon, Shane M., Jackson, Meyer B.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2018
• Subjects: Animals; Brain - physiology; Buffers; Calcium - analysis; Calcium - chemistry; calcium imaging; calcium sensors; Calcium Signaling - physiology; in vivo imaging; Neurons - physiology; Optical Imaging; two-photon microscopy; two-photon microscopy; in vivo imaging; calcium sensors; calcium imaging
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2018.09.005

Recent advances in Ca2+ imaging have given neuroscientists a tool to follow the activity of large numbers of individual neurons simultaneously in vivo in the brains of animals as they are presented with sensory stimulation, respond to environmental challenges, and engage in behaviors. The Ca2+ sensors used to transduce changes in cellular Ca2+ into changes in fluorescence must bind Ca2+ to produce a signal. By binding Ca2+, these sensors can act as buffers, often reducing the magnitude of a Ca2+ change severalfold, and producing a proportional slowing of the rates of change. Ca2+ probes can thus distort the patterns of activity they are intended to study and modify ongoing Ca2+ signaling functions. Recognizing these factors will enhance the use of in vivo Ca2+ imaging in the investigation of neural circuit function. Although the buffering actions of Ca2+ sensors are widely known, their magnitude and impact are often not fully appreciated. This buffering action will reduce the amplitude of a change in intracellular Ca2+ and prolong the decay. The magnitude of this buffering action is reflected in a sensor’s buffering capacity, which depends on the concentration and affinity of the sensor. The buffering capacity of a sensor exceeds the buffering capacity of endogenous Ca2+ buffers (Ca2+-binding proteins and metabolites) under the conditions that pertain during most Ca2+ imaging experiments. As a result, the Ca2+ sensor will have a dominant effect on Ca2+ signals. Recognizing the impact of the Ca2+ sensors used for Ca2+ imaging of intracellular Ca2+ will allow investigators to use these tools more effectively.