title: Characterization of voltage-gated K+ currents contributing to subthreshold membrane potential oscillations in hippocampal CA1 interneurons.
abstract: CA1 inhibitory interneurons at the stratum lacunosum-moleculare and radiatum junction (LM/RAD-INs) display subthreshold membrane potential oscillations (MPOs) involving voltage-dependent Na(+) and A-type K(+) currents. LM/RAD-INs also express other voltage-gated K(+) currents, although their properties and role in MPOs remain unclear. Here, we characterized these voltage-gated K(+) currents and investigated their role in MPOs. Using outside-out patch recordings from LM/RAD-IN somata, we distinguished four voltage-gated K(+) currents based on their pharmacology and activation/inactivation properties: a fast delayed rectifier current (I(Kfast)), a slow delayed rectifier current (I(Kslow)), a rapidly inactivating A-type current (I(A)), and a slowly inactivating current (I(D)). Their relative contribution to the total K(+) current was I(A) > I(Kfast) > I(Kslow) = I(D). The presence of I(D) and the relative contributions of K(+) currents in LM/RAD-INs are different from those of other CA1 interneurons, suggesting the presence of differential complement of K(+) currents in subgroups of interneurons. We next determined whether these K(+) currents were sufficient for MPO generation using a single-compartment model of LM/RAD-INs. The model captured the subthreshold voltage dependence of MPOs. Moreover, all K(+) currents were active at subthreshold potentials but I(D), I(A), and the persistent sodium current (I(NaP)) were most active near threshold. Using impedance analysis, we found that I(A) and I(NaP) contribute to MPO generation by modulating peak spectral frequency during MPOs and governing the voltage range over which MPOs occur. Our findings uncover a differential expression of a complement of K(+) channels that underlies intrinsic rhythmic activity in inhibitory interneurons.
authors.affiliation: Le Groupe de Recherche sur le Système Nerveux Central, Département de Physiologie, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: France
authors.initials: F
authors.lastname: Morin
authors.forename: Darrell
authors.initials: D
authors.lastname: Haufler
authors.forename: Frances K
authors.initials: FK
authors.lastname: Skinner
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lacaille
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001683:Biological Clocks / Q000502:physiology*; D055592:Biophysical Phenomena / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D004546:Elapid Venoms / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007395:Interneurons / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D008959:Models, Neurological; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D004546:Elapid Venoms; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D011189:Potassium Chloride; C020273:dendrotoxin; D015761:4-Aminopyridine; D001640:Bicuculline