EFFECTS OF CHARYBDOTOXIN ON K+ CHANNEL (KV1.2) DEACTIVATION AND INACTIVATION KINETICS

Of particular interest for voltage-gated K+ channels are the effects o f membrane voltage and pharmacologic agents on channel kinetics. We ha ve characterized in detail properties of a Kv1.2 channel expressed in oocytes as the basis for investigation of its structure-function relat ionships. This channel exhibited a voltage-dependent rate of activatio n with a V-1/2 of -21 mV. Voltage-dependent steady-state inactivation overlapped the activation curve with half-maximal inactivation occurri ng 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 activati on, charybdotoxin exhibited additional accumulation of block following activation, which was relieved with a time constant of 0.5 s upon rep olarization of the membrane. The deactivation of this channel was acce lerated in the presence of charybdotoxin while not significantly affec ted by dendrotoxin.