Brevetoxin modulates neuronal sodium channels in two cell lines derived from rat brain

Area of Science:

• Neuroscience
• Molecular Biology
• Toxicology

Background:

• Neuronal cell lines (B50, B104) from rat brain express sodium channels (Na+).
• Sodium channels are crucial for neuronal excitability and function.
• Brevetoxins are potent marine toxins affecting ion channels.

Purpose of the Study:

• To investigate the effects of brevetoxin (PbTx-3) on Na+ channel gating in B50 and B104 neuronal cell lines.
• To characterize modifications in Na+ channel activation, inactivation, and voltage dependence upon PbTx-3 exposure.

Main Methods:

• Single Na+ channel currents were recorded using cell-attached membrane patches.
• Neuronal cell lines (B50, B104) were exposed to purified brevetoxin (PbTx-3).
• Channel gating properties, including activation, inactivation, and voltage dependence, were analyzed before and after toxin exposure.

Main Results:

• PbTx-3 significantly increased the frequency of channel reopening, indicating slower inactivation.
• PbTx-3 altered voltage dependence, promoting channel opening near the resting potential (-60 to -50 mV).
• A 6.7 mV hyperpolarized shift in the threshold potential for channel opening was observed; slope conductance remained unchanged.

Conclusions:

• Brevetoxin (PbTx-3) modifies Na+ channel gating in rat neuronal cell lines.
• These modifications include slowed inactivation and altered voltage dependence, potentially leading to neuronal hyperexcitability.
• The observed effects suggest complex impacts of PbTx-3 on neuronal function in the intact brain.