title: Suppression of KV7/KCNQ potassium channel enhances neuronal differentiation of PC12 cells.
abstract: Membrane potential shift driven by electrical activity is critical in determining the cell fate of proliferation or differentiation. As such, the ion channels that underlie the membrane electrical activity play an important role in cell proliferation/differentiation. KV7/KCNQ potassium channels are critical in determining the resting membrane potentials in many neuronal cells. However, the role of these channels in cell differentiation is not well studied. In the present study, we used PC12 cells as well as primary cultured rat cortical neurons to study the role and mechanism of KV7/KCNQ in neuronal differentiation. NGF induced PC12 cell differentiation into neuron-like cells with growth of neurites showing typical growth cone-like extensions. The Kv7/KCNQ blocker XE991 promoted NGF-induced neurite outgrowth, whereas Kv7/KCNQ opener retigabine (RTG) inhibited outgrowth. M-type Kv7 channels are likely involved in regulating neurite growth because overexpression of KCNQ2/Q3 inhibited neurite growth whereas suppression of KCNQ2/Q3 with shRNA promoted neurite growth. Membrane depolarization possibly underpins enhanced neurite growth induced by the suppression of Kv7/KCNQ. Additionally, high extracellular K(+) likely induced membrane depolarization and also promoted neurite growth. Finally, T-type Ca(2+) channels may be involved in membrane-depolarization-induced neurite growth. This study provides a new perspective for understanding neuronal differentiation as well as KV7/KCNQ channel function.
authors.affiliation: Department of Pharmacology, Hebei Medical University, China; Department of Cell Biology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Najing
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Hebei Medical University, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Hebei Medical University, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Hebei Medical University, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Cell Biology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, Hebei Medical University, China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Pharmacology, Hebei Medical University, China. Electronic address: zhanghl@hebmu.edu.cn.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051658:KCNQ2 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D051659:KCNQ3 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D020748:Mibefradil / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D016716:PC12 Cells; D011188:Potassium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D020747:Calcium Channels, T-Type; D002491:Central Nervous System Agents; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; C496915:Kcnq2 protein, rat; C496918:Kcnq3 protein, rat; D012333:RNA, Messenger; D020748:Mibefradil; D009553:Nimodipine; D020932:Nerve Growth Factor; D011188:Potassium; D002118:Calcium
keywords: KV7/KCNQ potassium channel; differentiation; neurite; neuron