title: Gating, modulation and subunit composition of voltage-gated K(+) channels in dendritic inhibitory interneurones of rat hippocampus.
abstract: GABAergic interneurones are diverse in their morphological and functional properties. Perisomatic inhibitory cells show fast spiking during sustained current injection, whereas dendritic inhibitory cells fire action potentials with lower frequency. We examined functional and molecular properties of K(+) channels in interneurones with horizontal dendrites in stratum oriens-alveus (OA) of the hippocampal CA1 region, which mainly comprise somatostatin-positive dendritic inhibitory cells. Voltage-gated K(+) currents in nucleated patches isolated from OA interneurones consisted of three major components: a fast delayed rectifier K(+) current component that was highly sensitive to external 4-aminopyridine (4-AP) and tetraethylammonium (TEA) (half-maximal inhibitory concentrations < 0.1 mM for both blockers), a slow delayed rectifier K(+) current component that was sensitive to high concentrations of TEA, but insensitive to 4-AP, and a rapidly inactivating A-type K(+) current component that was blocked by high concentrations of 4-AP, but resistant to TEA. The relative contributions of these components to the macroscopic K(+) current were estimated as 57 +/- 5, 25 +/- 6, and 19 +/- 2 %, respectively. Dendrotoxin, a selective blocker of Kv1 channels had only minimal effects on K(+) currents in nucleated patches. Coapplication of the membrane-permeant cAMP analogue 8-(4-chlorophenylthio)-adenosine 3':5'-cyclic monophosphate (cpt-cAMP) and the phosphodiesterase blocker isobutyl-methylxanthine (IBMX) resulted in a selective inhibition of the fast delayed rectifier K(+) current component. This inhibition was absent in the presence of the protein kinase A (PKA) inhibitor H-89, implying the involvement of PKA-mediated phosphorylation. Single-cell reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed a high abundance of Kv3.2 mRNA in OA interneurones, whereas the expression level of Kv3.1 mRNA was markedly lower. Similarly, RT-PCR analysis showed a high abundance of Kv4.3 mRNA, whereas Kv4.2 mRNA was undetectable. This suggests that the fast delayed rectifier K(+) current and the A-type K(+) current component are mediated predominantly by homomeric Kv3.2 and Kv4.3 channels. Selective modulation of Kv3.2 channels in OA interneurones by cAMP is likely to be an important factor regulating the activity of dendritic inhibitory cells in principal neurone-interneurone microcircuits.
authors.affiliation: Physiologisches Institut der Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany.
authors.forename: Cheng-Chang
authors.initials: CC
authors.lastname: Lien
authors.forename: Marco
authors.initials: M
authors.lastname: Martina
authors.forename: Jobst H
authors.initials: JH
authors.lastname: Schultz
authors.forename: Heimo
authors.initials: H
authors.lastname: Ehmke
authors.forename: Peter
authors.initials: P
authors.lastname: Jonas
mesh_terms: D000200:Action Potentials; D000818:Animals; D051668:Delayed Rectifier Potassium Channels; D003712:Dendrites / Q000648:ultrastructure*; D004553:Electric Conductivity; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure*; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology* / Q000648:ultrastructure*; D015640:Ion Channel Gating; D007700:Kinetics; D009433:Neural Inhibition / Q000502:physiology*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051672:Shal Potassium Channels; D051670:Shaw Potassium Channels
chemical_list: D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D051670:Shaw Potassium Channels