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Gating currents from neuronal K(V)7.4 channels: general features and correlation with the ionic conductance
Francesco Miceli1, Maria Roberta Cilio, Maurizio Taglialatela
1Section of Pharmacology, Department of Neuroscience, University of Naples Federico II, Naples, Italy.
Channels (Austin, Tex.)
|August 20, 2009
Summary
This study investigated voltage-gated potassium (K(V)7) channels, focusing on how temperature affects their function. Researchers found that increased temperature accelerates K(V)7 channel kinetics and impacts gating currents, offering insights into channel gating mechanisms.
Area of Science:
- Molecular and Cellular Neuroscience
- Ion Channel Physiology
- Biophysics
Background:
- The K(V)7 (KCNQ) channel subfamily comprises five members (K(V)7.1-K(V)7.5), primarily expressed in cardiac and neuronal tissues.
- These channels are crucial for regulating neuronal excitability and cardiac rhythm through non-inactivating, slowly activating/deactivating currents.
- Understanding the gating mechanisms of K(V)7 channels is vital for interpreting disease-causing mutations and developing targeted therapeutics.
Purpose of the Study:
- To investigate the relationship between ionic currents and gating currents in homomeric neuronal K(V)7 channels (K(V)7.2-K(V)7.5).
- To determine the effect of temperature changes on the kinetics and voltage dependence of K(V)7 channel function.
- To characterize the properties of gating currents in K(V)7.4 and K(V)7.5 channels to elucidate the link between voltage-sensing domain movement and pore opening.
Main Methods:
- Utilized the cut-open oocyte voltage clamp technique.
- Recorded ionic currents and gating currents from homomeric K(V)7.2-K(V)7.5 channels.
- Blocked potassium (K(+)) conductance to isolate and study gating currents.
- Manipulated recording temperature between 18°C and 28°C.
Main Results:
- Increasing temperature from 18°C to 28°C accelerated activation/deactivation kinetics for all homomeric K(V)7 channels (K(V)7.2, K(V)7.3, K(V)7.4, K(V)7.5) without significantly altering voltage dependence.
- At 28°C, K(V)7.4 channels exhibited a significant increase in maximal ionic current amplitude.
- Gating currents were resolved for K(V)7.4 and K(V)7.5 channels, with distinct charge magnitudes (Q(ON) at +40 mV: 1.34 ± 0.34 nC for K(V)7.4; 0.79 ± 0.20 nC for K(V)7.5).
- K(V)7.4 gating currents at 28°C showed no charge immobilization, a left-shift in V(1/2) compared to G/V, faster Q(ON) decay than ionic current activation, and a rising phase in OFF gating charge post-depolarization.
Conclusions:
- Temperature significantly influences the gating kinetics of neuronal K(V)7 channels.
- In K(V)7.4 channels, voltage-sensing domain (VSD) movement is followed by a distinct, slow charge-transfer step preceding pore opening.
- These findings provide a mechanistic basis for understanding how mutations and drugs affect K(V)7 channel gating and function.
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