<p>Delayed-rectifier voltage-gated K<sup>+</sup> conductances (<i>I</i><sub>K</sub>) 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>I</i><sub>K</sub> 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>I</i><sub>K</sub> conductance and kinetics. 2. Analysis in the time domain revealed that for efficient modulation, the kinetics of <i>I</i><sub>K</sub> must correspond to that of the receptor current: slower-activating <i>I</i><sub>K</sub>s more strongly narrowed voltage responses elicited by slower receptor currents than faster-activating <i>I</i><sub>K</sub>s, 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>I</i><sub>K</sub>, and (2) attenuation of voltage response during its decay by excessive <i>I</i><sub>K</sub> due to its delayed deactivation. Consequently, the action of <i>I</i><sub>K</sub> 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>I</i><sub>K</sub> was limited to small voltage responses. Our results elucidate reciprocal relationships between the voltage response and <i>I</i><sub>K</sub>, and the conditions when <i>I</i><sub>K</sub> can confer band-pass properties to impedance gain function.</p>

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

  • Roman V. Frolov

摘要

Delayed-rectifier voltage-gated K+ conductances (IK) 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. IK 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 IK conductance and kinetics. 2. Analysis in the time domain revealed that for efficient modulation, the kinetics of IK must correspond to that of the receptor current: slower-activating IKs more strongly narrowed voltage responses elicited by slower receptor currents than faster-activating IKs, 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 IK, and (2) attenuation of voltage response during its decay by excessive IK due to its delayed deactivation. Consequently, the action of IK 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 IK was limited to small voltage responses. Our results elucidate reciprocal relationships between the voltage response and IK, and the conditions when IK can confer band-pass properties to impedance gain function.