Modulation of delayed rectifier potassium channel by protein kinase C zeta-containing signaling complex in pheochromocytoma cells.
Voltage-dependent delayed rectifier K(+) (Kv) channels are fundamental components in the regulation of neuronal excitability. We found that nerve growth factor (NGF) treatment of PC12 cells induced a hyperpolarizing shift of the Kv current activation curve by about 15 mV. This effect was similar to the effect of the modulatory subunit, Kv beta, on the cloned Kv channel, and required the activity of protein kinase C (PKC)zeta. Since NGF treatment of PC12 cells is known to increase the expression of p62 protein, which binds both to Kv beta and to PKC zeta, our results are consistent with the model in which p62 functions as a physical link in the assembly of signaling complex, PKC zeta-p62-Kv channel. In agreement with this model, the transient expression of p62 induced the same change in the Kv current activation curve as NGF, and the suppression of p62 expression inhibited the effect of NGF. The amount of bound Kv beta to p62 was increased by NGF treatment. These results suggest that the increased p62 protein induces the formation of the signaling complexes, enabling PKC zeta to modulate Kv channels. Thus, this may constitute a new way of modulating Kv channel activities.
Kim
Y
Y
Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
Uhm
D-Y
DY
Shin
J
J
Chung
S
S
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D051668:Delayed Rectifier Potassium Channels; D004347:Drug Interactions; D004553:Electric Conductivity; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015640:Ion Channel Gating; D008164:Luminescent Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal / Q000379:methods; D020932:Nerve Growth Factor / Q000494:pharmacology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D016716:PC12 Cells; D018408:Patch-Clamp Techniques / Q000379:methods; D010673:Pheochromocytoma / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011233:Precipitin Tests / Q000379:methods; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016601:RNA-Binding Proteins; D051381:Rats; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods
D048868:Adaptor Proteins, Signal Transducing; D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; D020319:Oligodeoxyribonucleotides, Antisense; C118585:P62 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D016601:RNA-Binding Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor; D011493:Protein Kinase C