GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20573902

From GONUTS
Jump to: navigation, search
Citation

Nadin, BM and Pfaffinger, PJ (2010) Dipeptidyl peptidase-like protein 6 is required for normal electrophysiological properties of cerebellar granule cells. J. Neurosci. 30:8551-65

Abstract

In cerebellar granule (CG) cells and many other neurons, A-type potassium currents play an important role in regulating neuronal excitability, firing patterns, and activity-dependent plasticity. Protein biochemistry has identified dipeptidyl peptidase-like protein 6 (DPP6) as an auxiliary subunit of Kv4-based A-type channels and thus a potentially important regulator of neuronal excitability. In this study, we used an RNA interference (RNAi) strategy to examine the role DPP6 plays in forming and shaping the electrophysiological properties of CG cells. DPP6 RNAi delivered by lentiviral vectors effectively disrupts DPP6 protein expression in CG cells. In response to the loss of DPP6, I(SA) peak conductance amplitude is reduced by >85% in parallel with a dramatic reduction in the level of I(SA) channel protein complex found in CG cells. The I(SA) channels remaining in CG cells after suppression of DPP6 show alterations in gating similar to Kv4 channels expressed in heterologous systems without DPP6. In addition to these effects on A-type current, we find that loss of DPP6 has additional effects on input resistance and Na(+) channel conductance that combine with the effects on I(SA) to produce a global change in excitability. Overall, DPP6 expression seems to be critical for the expression of a high-frequency electrophysiological phenotype in CG cells by increasing leak conductance, A-type current levels and kinetics, and Na(+) current amplitude.

Links

PubMed PMC2916862 Online version:10.1523/JNEUROSCI.5489-09.2010

Keywords

Action Potentials/physiology; Analysis of Variance; Blotting, Western; Cell Line; Cerebellum/cytology; Cerebellum/physiology; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism; Electrophysiology; Genetic Vectors; Hippocampus/cytology; Hippocampus/physiology; Humans; Lentivirus; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurons/physiology; Potassium Channels/genetics; Potassium Channels/metabolism; RNA Interference; Shal Potassium Channels/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:KCND2

acts_upstream_of_or_within

GO:0001508: action potential

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0001031)

Seeded From UniProt

complete

MOUSE:DPP6

acts_upstream_of_or_within

GO:0019228: neuronal action potential

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0001031)

Seeded From UniProt

complete

MOUSE:DPP6

acts_upstream_of_or_within

GO:0042391: regulation of membrane potential

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DPP6

acts_upstream_of_or_within

GO:0043266: regulation of potassium ion transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0001031)

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.