MODULATION OF SEPTAL CELL-ACTIVITY BY EXTRACELLULAR ZINC

ZINC released from axon terminals in the brain can interact with multi ple membrane channels and receptors. However, the specific effects of these Zn2+-dependent interactions on physiological processes remains u nclear. Because Zn2+-containing axon terminals are abundant in the sep tal region, we selected a septal cell line (SN56) to study the effects of Zn2+ on cell activity. Voltage-clamp recordings showed well-develo ped voltage-dependent Na+, Ca2+ and K+ currents. Micromolar concentrat ions of Zn2+ partially blocked Na+ and Ca2+ currents without affecting K+ currents. Current-clamp recordings showed that SN56 cells fire spo ntaneous and evoked action potentials. While most (greater than or equ al to 83%) Na+ and Co2+ currents were blocked with 1 mu M tetrodotoxin (TTX) and 2 mM Co2+, action potentials persisted after either 1 mu M TTX or 2 mM Co2+ application. In contrast, concentrations of Zn2+ (50- 300 mu M) that induced incomplete blockade (less than or equal to 50%) of either Ca2+ and Na+ currents abolished action potential generation . These data show that simultaneous and partial blockade of Ca2+ and N a+ channels by Zn2+ inhibit SN56 cell activity. Because septal outputs extensively modulate the excitability of cortical and subcortical bra in regions, Zn2+ inhibition of action potential generation in septal n eurons could play an important physiological role in regulating brain activity.