title: Modulation of delayed rectifier potassium channels by alpha1-adrenergic activation via protein kinase C zeta and p62 in PC12 cells.
abstract: When PC12 cells are exposed to nerve growth factor (NGF), they extend neurites and express autonomic ganglion cell properties. We have previously shown that NGF is capable of inducing p62 expression, enabling the formation of the protein kinase C zeta (PKCzeta)-p62-Kvbeta (beta-subunit of delayed rectifier K+ channel) complex, a Kv channel-modulating complex. The formation of this complex results in the shifting of the Kv channel activation curve to the left via PKCzeta activity. During the experiments, we noted that PC12 cells in a high-density culture exhibited a Kv channel activation curve shift similar to that observed in the NGF-treated cells. Therefore, we hypothesized that catecholamines released from PC12 cells may induce p62 expression. In order to test this idea, cells in a low-density culture were treated for 24h with norepinephrine (NE). In these cells, we noted a leftward shift of the activation curve. The presence of the alpha1-adrenergic antagonist specifically prevented the effects of NE. Pre-treatment of the low-density cells with alpha1-agonists induced changes similar to those associated with NE, confirming that NE modulates Kv channels via the alpha1-adrenergic receptor. NE's effects were blocked by treatment with PKCzeta specific inhibitors. Using Western blotting, we observed increased levels of p62 expression in both the high-density cells and the NE-treated low-density cells. These results suggest that locally secreted NE induces an increase in p62 expression, and also exerts a modulatory effect on Kv channels via the PKCzeta-p62-Kvbeta channel modulating complex.
authors.affiliation: Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Yonjung
authors.initials: Y
authors.lastname: Kim
authors.forename: Myung-Kyu
authors.initials: MK
authors.lastname: Park
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Uhm
authors.forename: Jaekyun
authors.initials: J
authors.lastname: Shin
authors.forename: Sungkwon
authors.initials: S
authors.lastname: Chung
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D016716:PC12 Cells; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000099221:Protein Kinase C zeta
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002352:Carrier Proteins; D002395:Catecholamines; D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors; D009638:Norepinephrine; D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C; D018340:Receptors, Adrenergic, alpha-1; D000099221:Protein Kinase C zeta