Both slow variants (GCaMP6s, jGCaMP7s) and fast variants (GCaMP6f, jGCaMP7f) are used in biological and neuroscience research. The slow variants are brighter and more sensitive to small changes in Ca levels, such as single action potentials; on the other hand, the fast variants are less sensitive but respond more quickly, making them useful for tracking changes in Ca levels over precise timescales. GCaMP6 also has a medium variant, GCaMP6m, whose kinetics are intermediate between GCaMP6s and GCaMP6f. Other variants of jGCaMP7 are also employed: jGCaMP7b exhibits bright baseline fluorescence and is used for imaging dendrites and axons, while jGCaMP7c exhibits greater contrast between maximal and baseline fluorescence and is advantageous for imaging large populations of neurons.
In 2018, Yang et al. reported the development of GCaMP-X, generated by the addition of a calmodulin-binding motif. Since the GCaMP calmodulin domain, when unbound, disrupts L-type calcium channel gating, the added calmodulin-binding motif prevents GCaMP-X from interfering with calcium-dependent signaling mechanisms.
In 2020, Zhang et al. reported the development of jGCaMP8, including sensitive, medium, and fast variants, which exhibit faster kinetics and greater sensitivity than the corresponding jGCaMP7 variants.
Red fluorescent indicators have also been developed: jRCaMP1a and jRCaMP1b use a circular permutation of the red fluorescent protein mRuby instead of GFP, while jRGECO1a is based on the red fluorescent protein mApple. Since the blue light used to excite GCaMP is scattered by tissue and the emitted green light is absorbed by blood, red fluorescent indicators provide more penetration and imaging depth in vivo than GCaMP. Use of red fluorescent indicators also avoids the photodamage caused by blue excitation light. Moreover, red fluorescent indicators allow for concurrent use of optogenetics, which is difficult with GCaMP because the excitation wavelengths of GCaMP overlap with those of channelrhodopsin-2 (ChR2). Simultaneous use of red and green GECIs can provide two-color visualization of different subcellular regions or cell populations.