title: Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cells.
abstract: Brief strong depolarization of cerebellar Purkinje cells produces a slow inward cation current [depolarization-induced slow current (DISC)]. Previous work has shown that DISC is triggered by voltage-sensitive Ca influx in the Purkinje cell and is attenuated by blockers of vesicular loading and fusion. Here, we have sought to characterize the ion channel(s) underlying the DISC conductance. While the brief depolarizing steps that triggered DISC were associated with a large Ca transient, the onset of DISC current corresponded only with the Ca transient decay phase. Furthermore, substitution of external Na with the impermeant cation N-methyl-d-glucamine produced a complete and reversible block of DISC, suggesting that the DISC conductance was not Ca permeant. Transient receptor potential cation channel, subfamily M, members 4 (TRPM4) and 5 (TRPM5) are nonselective cation channels that are opened by Ca transients but do not flux Ca. They are expressed in Purkinje cells of the posterior cerebellum, where DISC is large, and, in these cells, DISC is strongly attenuated by nonselective blockers of TRPM4/5. However, measurement of DISC currents in Purkinje cells derived from TRPM4 null, TRPM5 null, and double null mice as well as wild-type mice with TRPM4 short hairpin RNA knockdown showed a partial attenuation with 35-46% of current remaining. Thus, while the DISC conductance is Ca triggered, Na permeant, and Ca impermeant, suggesting a role for TRPM4 and TRPM5, these ion channels are not absolutely required for DISC.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Yu Shin
authors.initials: YS
authors.lastname: Kim
authors.forename: Eunchai
authors.initials: E
authors.lastname: Kang
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Makino
authors.forename: Sungjin
authors.initials: S
authors.lastname: Park
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Shin
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
authors.forename: Pierre
authors.initials: P
authors.lastname: Launay
authors.forename: David J
authors.initials: DJ
authors.lastname: Linden
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering; D012964:Sodium / Q000378:metabolism; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C505943:PD 140.548 N-methyl-D-glucamine; D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; C476766:TRPM4 protein, mouse; C498617:Trpm5 protein, mouse; D008536:Meglumine; D012964:Sodium; D002118:Calcium