title: On the role of calcium and potassium currents in circadian modulation of firing rate in rat suprachiasmatic nucleus neurons: multielectrode dish analysis.
abstract: The master circadian clock of mammals in the suprachiasmatic nucleus (SCN) of the hypothalamus entrains to a 24-h daily light-dark cycle and regulates circadian rhythms. The SCN is composed of multiple neurons with cell autonomous clocks exhibiting robust firing rhythms with a high firing rate during the subjective day. The membrane target(s) of the cellular clock responsible for circadian modulation of the firing rate in SCN neurons still remain unclear. Previously, L-type Ca(2+) currents and fast delayed rectifier (FDR) K(+) currents have been suggested to contribute directly to circadian modulation of electrical activity. Using long-term continuous recording of activity from dispersed rat SCN neurons in multielectrode dish and ionic channel blockers, we tested these hypotheses. Neither an L-type Ca(2+) current blocker (20 microM of nifedipine for 2 days) nor an FDR current blocker (500 microM of 4-aminopyridine (4-AP) for 4 days) suppressed the circadian modulation of firing rate. A specific blocker of Na(+) persistent current (5 microM of riluzole for 1 day followed by 10 microM during the next day) reversibly suppressed firing activity in a dose-dependent manner. These data indicate that neither nifedipine-sensitive Ca(2+) current(s) nor 4-AP-sensitive K(+) current(s) are key membrane targets for circadian modulation of electrical firing rate in SCN neurons.
authors.affiliation: Department of Physiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. NI.Kononenko@gmail.com
authors.forename: Nikolai I
authors.initials: NI
authors.lastname: Kononenko
authors.forename: Sato
authors.initials: S
authors.lastname: Honma
authors.forename: F Edward
authors.initials: FE
authors.lastname: Dudek
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Honma
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000295:instrumentation / Q000379:methods; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D026941:Sodium Channel Blockers