Shab K Channel Slow Inactivation. A Mechanism that Departs from Both C and U-Type Inactivation Mechanisms

Abstract

Once open Shab K channels inactivate within seconds. Shab slow inactivation presents characteristics that depart from both C and U-type mechanisms. Thus: Inactivation is facilitated by both external K+ and TEA, and the steady-state inactivation curve does not have a U-shape. Interestingly, the intracellular pore blocker quinidine inhibits open-state inactivation. In addition to inactivate from the open state Shab presents significant closed-state inactivation, which is also facilitated by extracellular K+. The time course of recovery from inactivation is the same regardless if channels inactivate from either the open or closed sates, indicating that in both cases they reach the same inactivated sate. The results herein presented combined with previous observations regarding the stability of GK in 0 K+ solutions at depolarized holding potentials, suggest that during Shab slow inactivation there is no closing or narrowing of the extracellular segment of the pore, capable to impede K+ movement. It seems instead that there is only a narrowing or rearrangement of the intracellular portion of the pore that extends to its central cavity and halts ion conduction.