title: Modulation of septal cell activity by extracellular zinc.
abstract: Zinc released from axon terminals in the brain can interact with multiple membrane channels and receptors. However, the specific effects of these Zn(2+)-dependent interactions on physiological processes remains unclear. Because Zn(2+)-containing axon terminals are abundant in the septal region, we selected a septal cell line (SN56) to study the effects of Zn2+ on cell activity. Voltage-clamp recordings showed well-developed voltage-dependent Na+, Ca2+ and K+ currents. Micromolar concentrations of Zn2+ partially blocked Na+ and Ca2+ currents without affecting K+ currents. Current-clamp recordings showed that SN56 cells fire spontaneous and evoked action potentials. While most (> or = 83%) Na+ and Ca2+ currents were blocked with 1 microM tetrodotoxin (TTX) and 2 mM Co2+, action potentials persisted after either 1 microM TTX or 2 mM Co2+ application. In contrast, concentrations of Zn2+ (50-300 microM) that induced incomplete blockade (< or = 50%) of either Ca2+ and Na+ currents abolished action potential generation. These data show that simultaneous and partial blockade of Ca2+ and Na+ channels by Zn2+ inhibit SN56 cell activity. Because septal outputs extensively modulate the excitability of cortical and subcortical brain regions, Zn2+ inhibition of action potential generation in septal neurons could play an important physiological role in regulating brain activity.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: L V
authors.initials: LV
authors.lastname: Colom
authors.forename: A
authors.initials: A
authors.lastname: Neely
authors.forename: M E
authors.initials: ME
authors.lastname: Diaz
authors.forename: W J
authors.initials: WJ
authors.lastname: Xie
authors.forename: S H
authors.initials: SH
authors.lastname: Appel
mesh_terms: D000200:Action Potentials / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects; D002460:Cell Line; D016015:Logistic Models; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D012688:Septum Pellucidum / Q000187:drug effects*; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D015032:Zinc