Correlation between charge movement and ionic current during slow inactivation in Shaker K+ channels

Area of Science:

• Molecular and Cellular Neuroscience
• Ion Channel Physiology
• Biophysics

Background:

• Potassium (K+) channels are crucial for neuronal excitability.
• Some K+ channels exhibit slow inactivation during prolonged depolarization.
• Fast (N-type) inactivation is mediated by the K+ channel amino terminus.

Purpose of the Study:

• Investigate the ionic and gating currents during long depolarizations in specific Shaker K+ channel mutants.
• Determine the voltage dependence of charge movement under depolarized conditions.
• Elucidate the mechanism underlying slow inactivation in K+ channels.

Main Methods:

• Utilized mutant Shaker H4-Delta(6-46) K+ channels and a nonconducting mutant (Shaker H4-Delta(6-46)-W434F) expressed in Xenopus oocytes.
• Employed cut-open oocyte and patch-clamp techniques to measure ionic and gating currents.
• Analyzed voltage dependence of charge movement and inactivation/recovery time courses.

Main Results:

• Prolonged depolarization shifted the voltage dependence of charge movement to more negative potentials.
• Both slow inactivation of ionic current and inactivation of gating current followed similar time courses.
• Recovery from inactivation for both ionic and gating currents also exhibited similar kinetics.
• A small fraction of channels remained non-inactivated, with unaltered voltage dependence.

Conclusions:

• Prolonged depolarization induces slow inactivation in Shaker K+ channels, affecting both ionic and gating currents.
• The voltage sensor conformation is modified during depolarization, leading to slow inactivation.
• A sequential model with parallel inactivated states can describe the observed phenomena.
• The findings provide insights into the gating mechanisms and inactivation processes of voltage-gated ion channels.