Rate-limiting Reactions Determining Different Activation Kinetics of Kv1.2and Kv2.1 Channels

Abstract

To identify the mechanisms underlying the faster activation kinetics in Kv1.2 channels compared to Kv2.1 channels, ionic and gating currents were studied in rat Kv1.2 and human Kv2.1 channels heterologously expressed in mammalian cells. At all voltages the time course of the ionic currents could be described by an initial sigmoidal and a subsequent exponential component and both components were faster in Kv1.2 than in Kv2.1 channels. In Kv1.2 channels, the activation time course was more sigmoid at more depolarized potentials, whereas in Kv2.1 channels it was somewhat less sigmoid at more depolarized potentials. In contrast to the ionic currents, the ON gating currents were similarly fast for both channels. The main portion of the measured ON gating charge moved before the ionic currents were activated. The equivalent gating charge of Kv1.2 ionic currents was twice that of Kv2.1 ionic currents, whereas that of Kv1.2 ON gating currents was smaller than that of Kv2.1 ON gating currents. In conclusion, the different activation kinetics of Kv1.2 and Kv2.1 channels are caused by rate-limiting reactions that follow the charge movement recorded from the gating currents. In Kv1.2 channels, the reaction coupling the voltage-sensor movement to the pore opening contributes to rate limitation in a voltage-dependent fashion, whereas in Kv2.1 channels, activation is additionally rate-limited by a slow reaction in the subunit gating.

Uncoupling Charge Movement from Channel Opening in Voltage-gated Potassium Channels by Ruthenium Complexes

“…5 and Table 1). Furthermore, linear models have been previously used satisfactorily in studies of Kv2.1 and other potassium channels (24,53,(63)(64)(65).…”

“…Albeit with some differences, most models and experimental data coincide in the sequential and independent activation of each of the four VSDs, which undergo transitions with high voltage dependence due to a large translocation of charge followed by one or more concerted transitions of all subunits, which lead to channel opening (18,20,22,23). Other Kv channels such as those from the Shab family, including Kv2.1 and Kv2.2, seem to share the main features of the gating mechanism found in Shaker (6,24), although detailed models are currently lacking.…”

Inhibition of Delayed Rectifier Potassium Channels and Induction of Arrhythmia

“…A clone for human Kv2.1 channels in pTracerSV40 vector was provided by Dr. T. Zimmer of Friedrich Schiller University (Jena, Germany) (14). HEK-293 cells expressing the channels were held at Ϫ80 mV, and 500-ms test pulses were applied in 10-mV increments.…”

Regulatory role of the extreme C‐terminal end of the S6 inner helix in C‐terminal‐truncated Kv1.2 channel activation

“…The Kv1.2 channel is a low‐threshold, rapidly activating voltage‐gated potassium channel in mammalian neurons (Stuhmer et al, 1989). It plays fundamental roles in generating electrical pulses and regulating membrane potential in brain and neuronal connections (Hoshi et al, 1990).…”