Kcnk5b potassium channel and calcineurin as a size rheostat in fin growth

Perathoner and colleagues (2014) used the zebrafish another longfin (alf) mutant to study size regulation in vertebrates. The mutant shows allometric growth, with proportionally enlarged fins and barbels.¹ They found that alf carries gain-of-function mutations in kcnk5b. In Xenopus oocytes, these mutations raised K+ conductance of the channel and hyperpolarized the cell.² Silic and Zhang (2023) describe longfin(lof t2) as the first reported zebrafish mutant with elongated fins. It is a dominant mutant that occurred in nature. Two independent reports traced it to Kcnh2a, a voltage-gated potassium channel.⁸

Perathoner and colleagues reported that the mutant channel acts locally in the mesenchyme of fins and barbels to increase appendage size.³ They also reported that the channel must be able to conduct K+ to cause this growth. Their genetic experiments suggested that kcnk5b may act independently of, or in parallel to, the gap junction gene cx43.⁴ George and Bates (2022) place the two genes side by side. Kcnk5b mutations enlarge fins, while connexin43 mutations shorten them. They read both as evidence that ion channel signalling regulates growth and proportion.⁷

Daane and colleagues (2018) started from a recent finding that calcineurin inhibitors change fin allometry. They identified Kcnk5b as a key player in integrating calcineurin's growth effects, in part through the cytoplasmic C-terminus of the channel. They proposed that the Kcnk5b and calcineurin interaction acts as a signaling node for allometric growth.⁵ Kcnk5b was required for the growth caused by calcineurin inhibition. The authors found that these factors specify fin growth independently of inherent cues of fin size and positional identity. They called the node a rheostat that integrates bioelectric and calcium-mediated signals.⁶

Silic and Zhang (2023) class the zebrafish fin and pigment mutations as indirect evidence for bioelectricity in patterning. In their view, direct tests became possible only with new voltage biosensors and manipulators.⁹ The fin work rests largely on mutants, channel recordings in oocytes and local transgenesis. These results show that K+ conductance affects size.² Silic and Zhang note a reported cellular voltage change, but they call the fin evidence indirect.⁹