Influence of the extracellular potassium concentration on the biophysical properties of KCNQ2, KCNQ3, and KCNQ5 voltage-gated potassium channels

Abstract

In the course of this investigation, properties of human KCNQ channels were investigated in different extracellular potassium concentrations (5 mM, 40 mM and 154 mM). Neuronal channel subunits and subunit compositions (KCNQ2, KCNQ3, KCNQ5, KCNQ2+3, KCNQ3+5) were heterologously expressed in CHO cells and analyzed in electrophysiological experiments using the patch-clamp technique. Biophysical properties of KCNQ channel current changed in elevated with respect to physiological extracellular potassium concentrations of 5 mM in the following manner: • A significant shift in voltage dependence of activation between 4-7 mV to more negative potentials could be found in 40 mM [K+]e for KCNQ2, KCNQ3 and KCNQ2+3 • A significant shift in voltage dependence of activation between 7-17 mV to more negative potentials could be found in 154 mM [K+]e for all KCNQ channels • A significant acceleration of activation and deactivation in 40 and 154 mM at potentials positive to -40 mV • A slowing in deactivation at potentials negative to -80 mV • An increase in whole-cell conductance could be found in all elevated [K+]e Methodological difficulties were investigated in order to correctly evaluate and interpret the outcome of the experiments in increasing extracellular potassium concentrations: • Amplitude and duration of potassium currents changed the potassium reversal potential during voltage-clamp experiments • The method of either analysing tail-currents or sustained-currents affected the interpretation of voltage dependence of activation • Series resistance errors remaining after electronic compensation could not be neglected in non-inactivating, experimentally overexpressed KCNQ-channel-currents The described changes in biophysical properties of KCNQ channels in increasing extracellular potassium concentration could be a mechanism to adapt the controlling function of KCNQ currents on cellular excitability in states such as repetitive neuronal firing and brain ischemia.