title: Modification of multiple ion channel functions in vivo by pharmacological inhibition: observation by threshold tracking and modeling.
abstract: Maintenance of axonal excitability relies on complex balance by multiple ion currents, but its evaluation is limited by in vitro single channel neurophysiological study on overall behavior. We sought to evaluate behaviors of multiple ion currents by pharmacological blockade. The threshold tracking technique was used to measure multiple excitability indices on tail sensory nerve of normal male mice before and after administration of either BaCl2or ivabradine. Mathematical modeling was used to identify the interval changes of the channel parameters. After administration of BaCl2and ivabradine, the following changes were present: greater threshold changes of both depolarizing and hyperpolarizing threshold electrotonus by both; additionally, reduced S2 accommodation, reduced late subexcitability and increased superexcitability by BaCl2, increased S3 accommodation by ivabradine. Mathematical modelling implied reduction of slow K+conductance, along with reduction of H conductance (Ih) by BaCl2; and reduction of Ih while augmentation of K+conductances by ivabradine. Pharmacological blockade of a selective ion channel may be compensated by other ion channels. Unintended effects by ion channel modification could be caused by secondary current alteration by multiple ion channels. J. Med. Invest. 64: 30-38, February, 2017.
authors.affiliation: Department of Neurology, Tokushima University.
authors.forename: Chimeglkham
authors.initials: C
authors.lastname: Banzrai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nodera
authors.forename: Ryo
authors.initials: R
authors.lastname: Okada
authors.forename: Saki
authors.initials: S
authors.lastname: Higashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Osaki
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism*; D017609:Barium Compounds / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077550:Ivabradine; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008959:Models, Neurological; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology
chemical_list: D017609:Barium Compounds; D001552:Benzazepines; D002712:Chlorides; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D026902:Potassium Channel Blockers; C024986:barium chloride; D000077550:Ivabradine