Ionic permeation and conduction properties of neuronal KCNQ2/KCNQ3 potassium channels.
Heteromeric KCNQ2/3 potassium channels are thought to underlie the M-current, a subthreshold potassium current involved in the regulation of neuronal excitability. KCNQ channel subunits are structurally unique, but it is unknown whether these structural differences result in unique conduction properties. Heterologously expressed KCNQ2/3 channels showed a permeation sequence of while showing a conduction sequence of A differential contribution of component subunits to the properties of heteromeric KCNQ2/3 channels was demonstrated by studying homomeric KCNQ2 and KCNQ3 channels, which displayed contrasting ionic selectivities. KCNQ2/3 channels did not exhibit an anomalous mole-fraction effect in mixtures of K(+) and Rb(+). However, extreme voltage-dependence of block by external Cs(+) was indicative of multi-ion pore behavior. Block of KCNQ2/3 channels by external Ba(2+) ions was voltage-independent, demonstrating unusual ionic occupation of the outer pore. Selectivity properties and block of KCNQ2 were altered by mutation of outer pore residues in a manner consistent with the presence of multiple ion-binding sites. KCNQ2/3 channel deactivation kinetics were slowed exclusively by Rb(+), whereas activation of KCNQ2/3 channels was altered by a variety of external permeant ions. These data indicate that KCNQ2/3 channels are multi-ion pores which exhibit distinctive mechanisms of ion conduction and gating.
Department of Pharmacology and MRC Centre for Synaptic Plasticity, University of Bristol, Bristol, United Kingdom.
David L
DL
Prole
Neil V
NV
Marrion
D001464:Barium / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002586:Cesium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D007668:Kidney / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D013329:Structure-Activity Relationship
D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D002586:Cesium; D001464:Barium; D011188:Potassium