期刊
ACTA PHARMACOLOGICA SINICA
卷 38, 期 9, 页码 1248-1256出版社
ACTA PHARMACOLOGICA SINICA
DOI: 10.1038/aps.2017.72
关键词
Kv7; KCNQ; M-current; prefrontal cortex; pyramidal neurons; excitability; mEPSC; retigabine; XE991; neuropsychiatric diseases
资金
- KeWei WANG from Ministry of Science and Technology of China [2013CB531302, 2014ZX09507003-006-004, 2013ZX09103001-015]
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 mu mol/L) or opener retigabine (10 mu mol/L) resulted in inhibition or activation of M-current, respectively. In the current-clamp recordings, inhibition of M-current was evidenced by the increased average spike frequency and the reduced first inter-spike interval (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.
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