Background: The KCa3.1 channel is the intermediate-conductance member of the Ca2+-
activated K channel superfamily. It is widely expressed in excitable and non-excitable cells, where
it plays a major role in a number of cell functions. This paper aims at illustrating the main structural,
biophysical and modulatory properties of the KCa3.1 channel, and providing an account of
experimental data on its role in volume regulation and Ca2+ signals.
Methods: Research and online content related to the structure, structure/function relationship, and
physiological role of the KCa3.1 channel are reviewed.
Results: Expressed in excitable and non-excitable cells, the KCa3.1 channel is voltage independent,
its opening being exclusively gated by the binding of intracellular Ca2+ to calmodulin, a Ca2+-
binding protein constitutively associated with the C-terminus of each KCa3.1 channel α subunit.
The KCa3.1 channel activates upon high affinity Ca2+ binding, and in highly coordinated fashion
giving steep Hill functions and relatively low EC50 values (100-350 nM). This high Ca2+ sensitivity
is physiologically modulated by closely associated kinases and phosphatases. The KCa3.1 channel
is normally activated by global Ca2+ signals as resulting from Ca2+ released from intracellular
stores, or by the refilling influx through store operated Ca2+ channels, but cases of strict functional
coupling with Ca2+-selective channels are also found. KCa3.1 channels are highly expressed in
many types of cells, where they play major roles in cell migration and death. The control of
these complex cellular processes is achieved by KCa3.1 channel regulation of the driving force for
Ca2+ entry from the extracellular medium, and by mediating the K+ efflux required for cell volume
Conclusion: Much work remains to be done to fully understand the structure/function relationship
of the KCa3.1 channels. Hopefully, this effort will provide the basis for a beneficial modulation of
channel activity under pathological conditions.