title: Effects of midazolam on ion currents and membrane potential in differentiated motor neuron-like NSC-34 and NG108-15 cells.
abstract: Midazolam (MDL) was known to act through stimulation of benzodiazepine receptors (GABA). Whether midazolam affects ion currents and membrane potential in neurons remains largely unclear. Electrophysiological studies of midazolam actions were performed in differentiated motor neuron-like (NSC-34 and NG108-15) cells. Midazolam suppressed the amplitude of delayed rectifier K(+) current (IK(DR)) in a time- and concentration-dependent manner with an IC50 value of 10.4 µM. Addition of midazolam was noted to enhance the rate of IK(DR) inactivation. On the basis of minimal binding scheme, midazolam-induced block of IK(DR) was quantitatively provided with a dissociation constant of 9.8 µM. Recovery of IK(DR) from inactivation in the presence of midazolam was fitted by a single exponential. midazolam had no effect on M-type or erg-mediated K(+) current in these cells. Midazaolam (30 µM) suppressed the peak amplitude of voltage-gated Na(+) current (INa) with no change in the current-voltage relationships of this current. Inactivation kinetics of INa remained unaltered in the presence of this agent. In current-clamp configuration, midazolam (30 µM) prolonged the duration of action potentials (APs) and reduce AP amplitude. Similarly, in differentiated NG108-15 cells, the exposure to midazolam also suppressed IK(DR) with a concomitant increase in current inactivation. Midazolam can act as an open-channel blocker of delayed-rectifier K(+) channels in these cells. The synergistic blocking effects on IK(DR) and INa may contribute to the underlying mechanisms through which midazolam affects neuronal function in vivo.
authors.affiliation: Department of Anesthesia, Tainan Municipal An-Nan Hospital, China Medical University, 66# Cheung Ho Road, An-Nan District, Tainan, Taiwan; Department of Anesthesia, China Medical University, 91# Hsueh-Shih Road, Taichung, Taiwan; Department of Cell Biology and Anatomy, Cheng Kung University, 1# University Road, Tainan City, Taiwan; Department of Anesthesia, Taishan Medical University, 619 Chang Cheng Road, Taian 271016, Shandong Province, PR China; Department of Anesthesia, Nan Shan branch of Gilu Hospital, Shandong University, Shandong Province, PR China. Electronic address: edmundsotw@gmail.com.
authors.forename: Edmund Cheung
authors.initials: EC
authors.lastname: So
authors.affiliation: Department of Anesthesiology, Eda-Hospital/I-Shou University, 1# Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, Taiwan. Electronic address: kingwutw@gmail.com.
authors.forename: King Chuen
authors.initials: KC
authors.lastname: Wu
authors.affiliation: Department of Orthopedic Surgery, E-Da Hospital/I-Shou University, 1# Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, Taiwan. Electronic address: ed100735@edah.org.tw.
authors.forename: Feng Chen
authors.initials: FC
authors.lastname: Kao
authors.affiliation: Department of Physiology, National Cheng Kung University, 1# University Road, Tainan City, Taiwan. Electronic address: snwu@mail.ncku.edu.tw.
authors.forename: Sheng Nan
authors.initials: SN
authors.lastname: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008691:Methadone / Q000494:pharmacology; D051379:Mice; D008874:Midazolam / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*
chemical_list: D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D008874:Midazolam; D008691:Methadone
keywords: Apamin (PubChem CID: 16218850); Delayed rectifier K(+) current; Flupirtine (PubChem CID : 53276); Membrane potential; Methadone (PubChem CID: 4095); Midazolam; Midazolam (PubChem CID: 4192); Motor neuron-like cells; Tetrodotoxin (PubChem CID: 11174599); Voltage-gated Na(+) current