Conversion of a delayed rectifier K+ channel to a voltage-gated inward rectifier K+ channel by three amino acid substitutions.

Single, double, and triple mutations progressively shift Shaker activation to more hyperpolarized potentials, resulting in an increase in the fraction of inactivated channels at negative resting voltages. The most negatively shifted mutation, the triple mutant, behaves like an inward rectifier. What is usually considered activation of an inward rectifier is, for the triple mutant, recovery from inactivation, and what is usually considered deactivation is inactivation. This conversion from outward rectifier to inward rectifier does not rely on a difference in sign or direction of charge movement of the voltage sensor, since activation of the Shaker outward rectifier is due to a different gate than activation of the triple mutant inward rectifier. Other voltage-dependent inward rectifiers in the Shaker family may work by a similar mechanism.