Gating currents from neuronal KV7.4 Channels: General features and correlation with the ionic conductance

Abstract

The KV7 (KCNQ) subfamily of voltage-gated K+ channels consists of five members (KV7.1- KV7.5) giving rise to non-inactivating, and slowly activating/deactivating currents mainly expressed in cardiac (KV7.1) and neuronal (KV7.2- KV7.5) tissue. In the present study, using the cut-open oocyte voltage clamp, we studied the relation of the ionic currents from homomeric neuronal Kv7 channels (KV7.2-KV7.5) with the gating currents recorded after K+ conductance blockade from the same channels. Increasing the recording temperature from 18{degree sign}C to 28{degree sign}C accelerated activation/deactivation kinetics of the ionic currents in all homomeric KV7 channels (activation Q10s at 0 mV were 3.8, 4.1, 8.3, and 2.8 for Kv7.2, Kv7.3, Kv7.4 and Kv7.5 channels, respectively), without large changes in currents voltage-dependence; moreover, at 28{degree sign}C, ionic currents carried by KV7.4 channels also showed a significant increase in their maximal value. Gating currents were only resolved in KV7.4 and KV7.5 channels; the size of the ON gating charges at +40 mV was 1.34 ± 0.34 nC for KV7.4, and 0.79 ± 0.20 nC for KV7.5. At 28{degree sign}C, KV7.4 gating currents had the following salient properties: 1) similar time integral of QON and QOFF, indicating no charge immobilization; 2) a left-shift in the V1/2 of the QON/V when compared to the G/V (≈ 50 mV in the presence of 2 mM extracellular Ba2+); 3) a QON decay faster than ionic current activation; and 4) a rising phase in the OFF gating charge after depolarizations larger than 0 mV. These observations suggest that, in KV7.4 channels, VSD movement is followed by a slow and/or low bearing charge step linking to pore opening, a result which may help to clarify the molecular consequence of disease-causing mutations and drugs affecting channel gating.