Key result
Mutant large conductance Ca2+-activated K+ channels lacking the RCK2 domain are nonfunctional despite tetramerization, highlighting the critical role of the RCK1-RCK2 hydrophobic interface.
The hydrophobic interface between RCK1 and RCK2 domains is essential for the Ca2+-dependent activation of large conductance Ca2+-activated K+ channels.
No clinical implications yet from this animal study; leaves open whether RCK1-RCK2 targeting could modulate BK channels in cardiovascular disease.
It has been suggested that the large conductance Ca(2)+-activated K(+) channel contains one or more domains known as regulators of K(+) conductance (RCK) in its cytosolic C terminus. Here, we show that the second RCK domain (RCK2) is functionally important and that it forms a heterodimer with RCK1 via a hydrophobic interface. Mutant channels lacking RCK2 are nonfunctional despite their tetramerization and surface expression. The hydrophobic residues that are expected to form an interface between RCK1 and RCK2, based on the crystal structure of the bacterial MthK channel, are well conserved, and the interactions of these residues were confirmed by mutant cycle analysis. The hydrophobic interaction appears to be critical for the Ca(2+)-dependent gating of the large conductance Ca(2+)-activated K(+) channel.
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Kim et al. (2006) studied this question. Mutant channels lacking RCK2 vs. Wild-type channels was evaluated on Channel function and tetramerization. Mutant large conductance Ca2+-activated K+ channels lacking the RCK2 domain are nonfunctional despite tetramerization, highlighting the critical role of the RCK1-RCK2 hydrophobic interface.
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