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Acute exposure to inorganic lead modifies high-threshold voltage-gated calcium currents in rat PC12 cells
1Department of Comparative Biosciences, University of Wisconsin, Madison 53706-1102, USA.
Abstract:
Acute exposure to 1, 10 and 50 microM lead acetate solutions irreversibly decreased calcium currents in 21 of 30 nerve growth factor-differentiated PC12 cells. In five cells, however, calcium currents irreversibly increased following lead exposure. Lead was equally effective at blocking the peak and sustained components of the calcium current. These data suggest complex interactions between neurotoxicologically relevant lead concentrations and high-threshold calcium currents in mammalian cells. They provide further support for the notion that at least one target of lead's toxic action is the voltage-gated calcium channel.
Insights
Lead acetate exposure altered calcium currents in PC12 cells, with most showing decreased currents and some showing increased currents. These findings suggest lead targets voltage-gated calcium channels.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Lead is a neurotoxin with known adverse effects on the nervous system.
- Voltage-gated calcium channels play crucial roles in neuronal function, including neurotransmitter release and cell signaling.
- PC12 cells, derived from a rat pheochromocytoma, are a widely used model for neuronal differentiation and function.
Purpose of the Study:
- To investigate the effects of acute lead acetate exposure on calcium currents in nerve growth factor-differentiated PC12 cells.
- To determine the concentration-dependent effects of lead on calcium influx.
- To elucidate the specific components of calcium currents affected by lead.
Main Methods:
- PC12 cells were differentiated using nerve growth factor.
- Cells were acutely exposed to varying concentrations of lead acetate (1, 10, and 50 microM).
- Whole-cell patch-clamp electrophysiology was used to measure voltage-gated calcium currents.
Main Results:
- Acute exposure to lead acetate (1, 10, 50 microM) resulted in irreversible decreases in calcium currents in 70% (21/30) of differentiated PC12 cells.
- In 16.7% (5/30) of cells, lead exposure led to an irreversible increase in calcium currents.
- Lead acetate effectively blocked both the peak and sustained components of the calcium current.
Conclusions:
- Lead acetate exerts complex, concentration-dependent effects on high-threshold calcium currents in mammalian PC12 cells.
- These findings support the hypothesis that voltage-gated calcium channels are a primary target of lead's neurotoxic action.
- The dual effect (decrease and increase) suggests intricate interactions between lead and calcium channel function.