Extracellular K+ elevates outward currents through Kir2.1 channels by increasing single-channel conductance

• Published in: Biochimica et biophysica acta 2011-06, Vol.1808 (6), p.1772-1778
• Main Authors: Liu, Tai-An, Chang, Hsueh-Kai, Shieh, Ru-Chi
• Format: Article
• Language: English
• Subjects: Algorithms; Animals; Binding, Competitive; Electric Conductivity; Excitability; Extracellular Space - metabolism; Female; Humans; Inward-rectification; Ion Channel Gating - physiology; Kinetics; Membrane Potentials - drug effects; Models, Biological; Oocytes - metabolism; Oocytes - physiology; Permeation; Potassium - metabolism; Potassium - pharmacology; Potassium Channels, Inwardly Rectifying - genetics; Potassium Channels, Inwardly Rectifying - physiology; Spermine - metabolism; Spermine - pharmacology; Time Factors; Xenopus
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2011.02.016

Outward currents through inward rectifier K+ channels (Kir) play a pivotal role in determining resting membrane potential and in controlling excitability in many cell types. Thus, the regulation of outward Kir current (IK1) is important for appropriate physiological functions. It is known that outward IK1 increases with increasing extracellular K+ concentration ([K+]o), but the underlying mechanism is not fully understood. A “K+-activation of K+-channel” hypothesis and a “blocking-particle” model have been proposed to explain the [K+]o-dependence of outward IK1. Yet, these mechanisms have not been examined at the single-channel level. In the present study, we explored the mechanisms that determine the amplitudes of outward IK1 at constant driving forces [membrane potential (Vm) minus reversal potential (EK)]. We found that increases in [K+]o elevated the single-channel current to the same extent as macroscopic IK1 but did not affect the channel open probability at a constant driving force. In addition, spermine-binding kinetics remained unchanged when [K+]o ranged from 1 to 150mM at a constant driving force. We suggest the regulation of K+ permeation by [K+]o as a new mechanism for the [K+]o-dependence of outward IK1. ► We study the regulation of outward Kir2.1 currents by [K+]o. ► [K+]o up-regulates single-channel conductance but not open probability. ► [K+]o-effect on outward Kir2.1 currents is not related to relief of channel block. ► [K+]o directly modulates K+ permeation in Kir2.1 channels.