INACTIVATION OF KV2.1 POTASSIUM CHANNELS

We report here several unusual features of inactivation of the rat Kv2 .1 delayed rectifier potassium channel, expressed in Xenopus oocytes. The voltage dependence of inactivation was U-shaped, with maximum inac tivation near 0 mV. During a maintained depolarization, development of inactivation was slow and only weakly voltage dependent (tau = 4 s at 0 mV; tau = 7 s at +80 mV). However, recovery from inactivation was s trongly voltage dependent (e-fold for 20 mV) and could be rapid (tau = 0.27 s at -140 mV). Kv2.1 showed cumulative inactivation, where inact ivation built up during a train of brief depolarizations. A single mai ntained depolarization produced more steady-state inactivation than a train of pulses, but there could actually be more inactivation with th e repeated pulses during the first few seconds. We term this phenomeno n ''excessive cumulative inactivation.'' These results can be explaine d by an allosteric model, in which inactivation is favored by activati on of voltage sensors, but the open state of the channel is resistant to inactivation.