U-type inactivation of Kv3.1 and Shaker potassium channels

We previously concluded that the Kv2.1 K(+) channel inactivates preferentially from partially activated closed states. We report here that the Kv3.1 channel also exhibits two key features of this inactivation mechanism: a U-shaped voltage dependence measured at 10 s and stronger inactivation with repetitive pulses than with a single long depolarization. More surprisingly, slow inactivation of the Kv1 Shaker K(+) channel (Shaker B Delta 6--46) also has a U-shaped voltage dependence for 10-s depolarizations. The time and voltage dependence of recovery from inactivation reveals two distinct components for Shaker. Strong depolarizations favor inactivation that is reduced by K(o)(+) or by partial block by TEA(o), as previously reported for slow inactivation of Shaker. However, depolarizations near 0 mV favor inactivation that recovers rapidly, with strong voltage dependence (as for Kv2.1 and 3.1). The fraction of channels that recover rapidly is increased in TEA(o) or high K(o)(+). We introduce the term U-type inactivation for the mechanism that is dominant in Kv2.1 and Kv3.1. U-type inactivation also makes a major but previously unrecognized contribution to slow inactivation of Shaker.