title: Contribution of slowly inactivating potassium current to delayed firing of action potentials in NG108-15 neuronal cells: experimental and theoretical studies.
abstract: The properties of slowly inactivating delayed-rectifier K+ current (I(K)(dr)) were investigated in NG108-15 neuronal cells differentiated with long-term exposure to dibutyryl cyclic AMP. Slowly inactivating I(K)(dr) could be elicited by prolonged depolarizations from -50 to +50 mV. These outward K+ currents were found to decay at potentials above -20 mV, and the decay became faster with greater depolarization. Cell exposure to aconitine resulted in the reduction of I(K)(dr) amplitude along with an accelerated decay of current inactivation. Under current-clamp recordings, a delay in the initiation of action potentials (APs) in response to prolonged current stimuli was observed in these cells. Application of aconitine shortened the AP initiation in combination with an increase in both width of spike discharge and firing frequency. The computer model, in which state-dependent inactivation of I(K)(dr) was incorporated, was also implemented to predict the firing behavior present in NG108-15 cells. As the inactivation rate constant of I(K)(dr) was elevated, the firing frequency was progressively increased along with a shortening of the latency for AP appearance. Our theoretical work and the experimental results led us to propose a pivotal role of slowly inactivating I(K)(dr) in delayed firing of APs in NG108-15 cells. The results also suggest that aconitine modulation of I(K)(dr) gating is an important molecular mechanism through which it can contribute to neuronal firing.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan. snwu@mail.ncku.edu.tw
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Wu
authors.forename: Bing-Shuo
authors.initials: BS
authors.lastname: Chen
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Yen-Chin
authors.initials: YC
authors.lastname: Liu
mesh_terms: D000157:Aconitine / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D003198:Computer Simulation; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D051668:Delayed Rectifier Potassium Channels; D015222:Sodium Channels; D000157:Aconitine