title: Modification of activation kinetics of delayed rectifier K+ currents and neuronal excitability by methyl-β-cyclodextrin.
abstract: The effects of methyl-β-cyclodextrin (MβCD), an oligosaccharide, on ion currents were investigated in differentiated NG108-15 neuronal cells. In NG108-15 cells treated with dibutyryl cyclic AMP, the expression level of the K(V)3.1 mRNA was elevated. Depletion of membrane cholesterol by exposing cells to MβCD (1 mM) resulted in a significant reduction of the activation kinetics of delayed rectifier K(+) current (I(K)((DR))) in these cells. However, neither activation nor inactivation curve of I(K(DR)) was altered following MβCD treatment. In current-clamp recordings, in MβCD-treated cells, the instantaneous frequency of the firing in response to long-lasting current stimuli was reduced. In a modified Hodgkin-Huxley neuron, the upward shift in the relationship of activation/deactivation time constant of I(K(DR)) versus membrane potential causes a reduction of I(K(DR)) amplitude accompanied by an increase in the width of action potentials. In the studies from a high-frequency modeled neuron, reduction of voltage-dependent activation of I(K(DR)) can also facilitate spike-frequency adaptation. In a simulated network of spiking neurons, the increased activation/deactivation time constant of I(K(DR)) slowed repetitive firing. Taken together, MβCD may slow activation kinetics of I(K(DR)) and confer a trigger for the propensity to develop spike-frequency adaptation in neurons or neuroendocrine cells.
authors.affiliation: Department of Neurology, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: C-W
authors.initials: CW
authors.lastname: Huang
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Wu
authors.forename: S-N
authors.initials: SN
authors.lastname: Wu
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002460:Cell Line; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008962:Models, Theoretical; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051670:Shaw Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology*
chemical_list: D051670:Shaw Potassium Channels; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin