Evidence for cooperative interactions in potassium channel gating

CLONING and expression of voltage-activated potassium ion-channel complementary DNAs1–4 has confirmed that these channels are composed of four identical subunits5, each containing a voltage sensor. It has been generally accepted that the voltage sensors must reach a permissive state through one or more confor-mational ('gating') transitions before the channel can open6,7. To test whether each subunit gates independently, we have constructed cDNAs encoding four subunits on a single polypeptide chain, enabling us to specify the subunit stoichiometry. The gating of heterotetramers made up from combinations of subunits with different gating phenotypes strongly suggests that individual sub-units gate cooperatively, rather than independently8. Nonindependent subunit gating is consistent with measurements of the kinetics of K+-channel gating currents9–13 and in line with the widespread subunit cooperativity observed in other multisubunit proteins14.