We have investigated the actions of internal and external Zn2+ on squi
d axon K channel ionic and gating currents. As has been noted previous
ly, application of Zn2+ to either membrane surface substantially slowe
d the activation of these channels with little or no change in deactiv
ation. internal Zn2+ (near 200-300 nM) slowed channel activation by up
to sixfold over the range of membrane voltages from -30 to +50 mV. Ex
ternal Zn2+ (10 mM) produced an approximate twofold slowing of activat
ion from -40 to +40 mV. We found that the changes in ionic current act
ivation kinetics were accompanied by less than a twofold slowing of ch
annel-gating currents in a narrow range of potentials near -30 mV. The
re was, at most, only a few percent reduction of charge movement assoc
iated with Zn2+ application. We conclude that these ions interact with
channel components involved in weakly voltage-dependent conformationa
l changes. Although there are some differences in detail, the general
similarity of the actions of both internal and external Zn2+ on channe
l function suggests that the modified channel-gating step involves ami
no acids accessible to both the internal and external membrane surface
.