Formation of intermediate-conductance calcium-activated potassium channels
by interaction of Slack and Slo subunits
William J. Joiner1, 3, Michael D. Tang1, 3, Lu-Yang Wang1, Steven I. Dworetzky2, Christopher G. Boissard2, Li Gan1, Valentin K. Gribkoff2
& Leonard K. Kaczmarek1
1
Departments of Pharmacology and Cellular and Molecular
Physiology, Yale University School of Medicine, Cedar Street, New Haven, Connecticut 06520, USA
2
Neurosciences Drug Discovery, Bristol-Myers Squibb
Pharmaceutical Research Institute, 5 Research Parkway,
Wallingford, Connecticut 06492, USA
3
W.J.J. and M.D.T. contributed equally to this work
Correspondence should be addressed to Leonard K. Kaczmarek kaczmarek@yale.edu
Large-conductance calcium-activated potassium channels (maxi-K channels)
have an essential role in the control of excitability and secretion. Only
one gene Slo is known to encode maxi-K channels, which are sensitive
to both membrane potential and intracellular calcium. We have isolated a potassium
channel gene called Slack that is abundantly expressed in the nervous
system. Slack channels rectify outwardly with a unitary conductance of about
25−65 pS and are inhibited by intracellular calcium. However, when Slack is co-expressed with Slo, channels with pharmacological properties
and single-channel conductances that do not match either Slack or Slo are
formed. The Slack/Slo channels have intermediate conductances of about 60−180
pS and are activated by cytoplasmic calcium. Our findings indicate that some
intermediate-conductance channels in the nervous system may result from an
interaction between Slack and Slo channel subunits.
