A novel DPP6 isoform (DPP6-E) can account for differences between neuronal and reconstituted A-type K(+) channels.
The channels mediating most of the somatodendritic A-type K(+) current in neurons are thought to be ternary complexes of Kv4 pore-forming subunits and two types of auxiliary subunits, the K(+) channel interacting proteins (KChIPs) and dipeptidyl-peptidase-like (DPPL) proteins. The channels expressed in heterologous expression systems by mixtures of Kv4.2, KChIP1 and DPP6-S resemble in many properties the A-type current in hippocampal CA1 pyramidal neurons and cerebellar granule cells, neurons with prominent A-type K(+) currents. However, the native currents have faster kinetics. Moreover, the A-type currents in neurons in intermediary layers of the superior colliculus have even faster inactivating rates. We have characterized a new DPP6 spliced isoform, DPP6-E, that produces in heterologous cells ternary Kv4 channels with very fast kinetics. DPP6-E is selectively expressed in a few neuronal populations in brain including cerebellar granule neurons, hippocampal pyramidal cells and neurons in intermediary layers of the superior colliculus. The effects of DPP6-E explain past discrepancies between reconstituted and native Kv4 channels in some neurons, and contributes to the diversity of A-type K(+) currents in neurons.
Maffie
Jonathon
J
Department of Physiology & Neuroscience, New York University School of Medicine, New York, NY 10016, USA.
Blenkinsop
Timothy
T
Rudy
Bernardo
B
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002461:Cell Line, Transformed; D003001:Cloning, Molecular / Q000379:methods; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007700:Kinetics; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010447:Peptide Hydrolases / Q000235:genetics* / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods
D051605:Kv Channel-Interacting Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D020033:Protein Isoforms; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D049452:Green Fluorescent Proteins; C503535:DPP6 protein, human; D010447:Peptide Hydrolases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases