Voltage-gated K+ channels play a role in cAMP-stimulated neuritogenesis in mouse neuroblastoma N2A cells.
Neuritogenesis is essential in establishing the neuronal circuitry. An important intracellular signal causing neuritogenesis is cAMP. In this report, we showed that an increase in intracellular cAMP stimulated neuritogenesis in neuroblastoma N2A cells via a PKA-dependent pathway. Two voltage-gated K(+) (Kv) channel blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA), inhibited cAMP-stimulated neuritogenesis in N2A cells in a concentration-dependent manner that remarkably matched their ability to inhibit Kv currents in these cells. Consistently, siRNA knock down of Kv1.1, Kv1.4, and Kv2.1 expression reduced Kv currents and inhibited cAMP-stimulated neuritogenesis. Kv1.1, Kv1.4, and Kv2.1 channels were expressed in the cell bodies and neurites as shown by immunohistochemistry. Microfluorimetric imaging of intracellular [K(+)] demonstrated that [K(+)] in neurites was lower than that in the cell body. We also showed that cAMP-stimulated neuritogenesis may not involve voltage-gated Ca(2+) or Na(+) channels. Taken together, the results suggest a role of Kv channels and enhanced K(+) efflux in cAMP/PKA-stimulated neuritogenesis in N2A cells.
Leung
Yuk-Man
YM
Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan. ymleung@mail.cmu.edu.tw
Huang
Chien-Fang
CF
Chao
Chia-Chia
CC
Lu
Dah-Yuu
DY
Kuo
Chang-Shin
CS
Cheng
Tzu-Hurng
TH
Chang
Li-Yun
LY
Chou
Chun-Hsiao
CH
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology
D015220:Calcium Channels; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D047428:Protein Kinase Inhibitors; D015222:Sodium Channels; D005576:Colforsin; D014634:Valinomycin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015056:1-Methyl-3-isobutylxanthine