Analysis of inductance-like effects of delayed rectifiers: amplification of voltage response onset, acceleration of decay, and voltage- and kinetics-dependent limitations.

Abstract

Delayed-rectifier voltage-gated K⁺ conductances (I_K) can confer band-pass properties to the membrane impedance gain function in the frequency domain, and shorten the duration of transient receptor potentials evoked by voltage-insensitive receptor currents in the time domain. Here, by investigating in silico the underlying mechanisms, we found that: 1. I_K activation rate was the major determinant of both the voltage response narrowing and the impedance gain peaking. Both effects were non-linear, voltage-dependent, with the maxima determined by I_K conductance and kinetics. 2. Analysis in the time domain revealed that for efficient modulation, the kinetics of I_K must correspond to that of the receptor current: slower-activating I_Ks more strongly narrowed voltage responses elicited by slower receptor currents than faster-activating I_Ks, and vice versa. 3. Two complementary mechanisms mediated the modulation: (1) voltage amplification at the onset of receptor current during a window of relatively high resistance due to delayed activation of I_K, and (2) attenuation of voltage response during its decay by excessive I_K due to its delayed deactivation. Consequently, the action of I_K caused a partial leftward shift of voltage waveform relative to the receptor current, resembling the effect of electrical inductance. 4. Voltage response narrowing was opposed by self-shunting of the depolarizing receptor current as it increased. Consequently, the increase in corner frequency due to I_K was limited to small voltage responses. Our results elucidate reciprocal relationships between the voltage response and I_K, and the conditions when I_K can confer band-pass properties to impedance gain function.