Modulation of septal cell activity by extracellular zinc

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.