EVIDENCE FOR COOPERATIVE INTERACTIONS IN POTASSIUM CHANNEL GATING

CLONING and expression of voltage-activated potassium ionchannel 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 conformational ('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 subunits 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.