Gating currents from neuronal K(V)7.4 channels: general features and correlation with the ionic conductance

Abstract

The K(V)7 (KCNQ) subfamily of voltage-gated K(+) channels consists of five members (K(V)7.1-K(V)7.5) giving rise to non-inactivating, and slowly activating/deactivating currents mainly expressed in cardiac (K(V)7.1) and neuronal (K(V)7.2-K(V)7.5) tissue. In the present study, using the cut-open oocyte voltage clamp, we studied the relation of the ionic currents from homomeric neuronal K(V)7 channels (K(V)7.2-K(V)7.5) with the gating currents recorded after K(+) conductance blockade from the same channels. Increasing the recording temperature from 18 degrees C to 28 degrees C accelerated activation/deactivation kinetics of the ionic currents in all homomeric K(V)7 channels (activation Q(10)s at 0 mV were 3.8, 4.1, 8.3 and 2.8 for K(V)7.2, K(V)7.3, K(V)7.4 and K(V)7.5 channels, respectively), without large changes in currents voltage-dependence; moreover, at 28 degrees C, ionic currents carried by K(V)7.4 channels also showed a significant increase in their maximal value. Gating currents were only resolved in K(V)7.4 and K(V)7.5 channels; the size of the ON gating charges at +40 mV was 1.34 +/- 0.34 nC for K(V)7.4, and 0.79 +/- 0.20 nC for K(V)7.5. At 28 degrees C, K(V)7.4 gating currents had the following salient properties: (1) similar time integral of Q(ON) and Q(OFF), indicating no charge immobilization; (2) a left-shift in the V(1/2) of the Q(ON)/V when compared to the G/V (approximately 50 mV in the presence of 2 mM extracellular Ba(2+)); (3) a Q(ON) 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 K(V)7.4 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.