Pharmacological modulation of the voltage-gated neuronal Kv7/KCNQ/M-channel alters the intrinsic excitability and synaptic responses of pyramidal neurons in rat prefrontal cortex slices

• Published in: Acta pharmacologica Sinica Vol. 38; no. 9; pp. 1248 - 1256
• Main Authors: Peng, Hui, Bian, Xi-ling, Ma, Fu-cui, Wang, Ke-Wei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2017; Nature Publishing Group
• Subjects: Afterhyperpolarization; Alzheimer's disease; Animals; Anthracenes - chemistry; Anthracenes - pharmacology; Biomedical and Life Sciences; Biomedicine; Brain slice preparation; Cognitive ability; Data processing; Depression; Dose-Response Relationship, Drug; Excitability; Excitatory postsynaptic potentials; Immunology; Internal Medicine; KCNQ Potassium Channels - antagonists & inhibitors; KCNQ Potassium Channels - metabolism; Latency; Male; Medical Microbiology; Membrane potential; Mental depression; Mental disorders; Neurodegenerative diseases; Neuromodulation; Original; original-article; Pharmacology/Toxicology; Potassium Channel Blockers - chemistry; Potassium Channel Blockers - pharmacology; Potassium channels (voltage-gated); Prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Pyramidal cells; Pyramidal Cells - drug effects; Pyramidal Cells - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Schizophrenia; Structure-Activity Relationship; Synaptic transmission; Synaptic Transmission - drug effects; Vaccine; Voltage; 兴奋性突触后电位; 前额叶皮质; 反应; 大鼠; 电压门控; 调制; 通道; 锥体神经元; excitability; retigabine; prefrontal cortex; KCNQ; pyramidal neurons; mEPSC; XE991; Kv7; neuropsychiatric diseases; M-current
• DOI: 10.1038/aps.2017.72
• ISSN: 1671-4083; 1745-7254

The prefrontal cortex （PFC） critical for higher cognition is implicated in neuropsychiatric diseases, such as Alzheimer＇s disease, depression and schizophrenia. The voltage-activated Kv7/KCNQ/M-channel or M-current modulates the neuronal excitability that defines the fundamental mechanism of brain function. However, whether M-current functions to regulate the excitability of PFC neurons remains elusive. In this study, we recorded the native M-current from PFC layer V pyramidal neurons in rat brain slices and showed that it modulated the intrinsic excitability and synaptic responses of PFC pyramidal neurons. Application of a specific M-channel blocker XE991 （40 pmol/L） or opener retigabine （10 pmol/L） resulted in inhibition or activation of M-current, respectively. In the currentclamp recordings, inhibition of M-current was evidenced by the increased average spike frequency and the reduced first inter-spike intervat （ISI）, spike onset latency and fast afterhyperpolarization （fAHP）, whereas activation of M-current caused opposite responses. Furthermore, inhibition of M-current significantly increased the amplitude of excitatory postsynaptic potentials （EPSPs） and depolarized the resting membrane potential （RMP） without affecting the miniature EPSC （mEPSC） frequency. These data demonstrate that voltage-gated neuronal Kv7/KCNQ/M-current modulates the excitability and synaptic transmission of PFC neurons, suggesting that pharmacological modulation of M-current in the PFC may exert beneficial effects on cognitive deficits implicated in the pathophysiology of neuropsychiatric disorders.