title: The effects of ion channel blockers validate the conductance-based model of saccadic oscillations.
abstract: Conductance-based models of reciprocally inhibiting burst neurons suggest that intrinsic membrane properties and postinhibitory rebound (PIR) determine the amplitude and frequency of saccadic oscillations. Reduction of the low-threshold calcium currents (I(T)) in the model decreased the amplitude but increased the frequency of the simulated oscillations. Combined reduction of hyperpolarization-activated cation current (I(h)) and I(T) in the model abolished the simulated oscillations. We measured the effects of a selective blocker of I(T) (ethosuximide) in healthy subjects on the amplitude and frequency of saccadic oscillations evoked by eye closure and of a nonselective blocker of I(h) and I(T) (propronolol) in a patient with microsaccadic oscillation and limb tremor syndrome (mSOLT). Ethosuximide significantly reduced the amplitude but increased the frequency of the saccadic oscillations during eye closure in healthy subjects. Propranolol abolished saccadic oscillations in the mSOLT patient. These results support the hypothetical role of postinhibitory rebound, I(h), and I(T) , in generation of saccadic oscillations and determining their kinematic properties.
authors.affiliation: Department of Neurology, Case Western Reserve University, Cleveland, Ohio 44106-5040, USA.aasefshaikh@gmail.com
authors.forename: Aasef G
authors.initials: AG
authors.lastname: Shaikh
authors.forename: David S
authors.initials: DS
authors.lastname: Zee
authors.forename: Lance M
authors.initials: LM
authors.lastname: Optican
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Miura
authors.forename: Stefano
authors.initials: S
authors.lastname: Ramat
authors.forename: R John
authors.initials: RJ
authors.lastname: Leigh
mesh_terms: D016022:Case-Control Studies; D005013:Ethosuximide / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology; D015835:Ocular Motility Disorders / Q000503:physiopathology; D011433:Propranolol / Q000494:pharmacology; D012438:Saccades / Q000187:drug effects* / Q000502:physiology*; D013577:Syndrome; D014202:Tremor / Q000503:physiopathology
chemical_list: D007473:Ion Channels; D005013:Ethosuximide; D011433:Propranolol