Effects of charybdotoxin on K+ channel (Kv1.2) deactivation and inactivation kinetics

Of particular interest for voltage-gated K+ channels are the effects of membrane voltage and pharmacologic agents on channel kinetics. We have characterized in detail properties of a Kv1.2 channel expressed in oocytes as the basis for investigation of its structure-function relationships. This channel exhibited a voltage-dependent rate of activation with a V-1/2 of -21 mV. Voltage-dependent steady-state inactivation overlapped the activation curve with half-maximal inactivation occurring at -22 mV. Dendrotoxin inhibited channel activation with an IC50 of 8.6 nM at + 35 mV. Charybdotoxin also blocked this K+ channel (IC50 = 5.6 nM). While dendrotoxin block was not affected by channel activation, charybdotoxin exhibited additional accumulation of block following activation, which was relieved with a time constant of 0.5 s upon repolarization of the membrane. The deactivation of this channel was accelerated in the presence of charybdotoxin while not significantly affected by dendrotoxin.