Phorbol esters block a voltage-sensitive chloride current in hippocampal pyramidal cells

Area of Science:

• Neuroscience
• Cellular Physiology

Background:

• Second-messenger systems modulate neuronal excitability via ionic conductances.
• Cyclic AMP and protein kinase A are established modulators.
• Protein kinase C activation is increasingly recognized for its modulatory role.

Purpose of the Study:

• To investigate novel ionic currents in hippocampal pyramidal cells.
• To explore the role of protein kinase C in modulating neuronal currents.
• To identify new mechanisms regulating neuronal excitability.

Main Methods:

• Electrophysiological recordings in hippocampal pyramidal cells.
• Pharmacological activation of protein kinase C using phorbol esters.
• Analysis of voltage-dependent ionic currents.

Main Results:

• A previously undescribed voltage-dependent chloride current was identified in hippocampal pyramidal cells.
• This chloride current is active at resting potential.
• The current is inhibited by membrane depolarization and protein kinase C activation.

Conclusions:

• A novel chloride current contributes to regulating hippocampal pyramidal cell excitability.
• Protein kinase C activation inhibits this chloride current, suggesting a regulatory role.
• The current may be localized to dendritic membranes, influencing dendritic excitability.