The gating of different potassium channels depends on many diverse factors.
We now report a unique example of a K+ channel with a Cl- dependence. The
slo-2 gene was cloned from Caenorhabditis elegans and is widely expressed i
n both neurons and muscles; it was highly abundant, as suggested by its hig
h representation in the C. elegans EST database. SLO-2, like its paralogue,
SLO-1, was also dependent on Ca2+. We show by site-directed mutagenesis th
at its requirements for both Cl- and Ca2+ are synergistic and associated wi
th the same functional domain. SLO-2's dependence on Cl- implies that intra
cellular Cl- homeostasis may be important in regulating cellular excitabili
ty through this unusual K+ channel.