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

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Abstract
The importance of second-messenger systems in controlling the excitability of neurones and other cells, through modulation of voltage- and calcium-dependent ionic conductances, has become increasingly clear. Cyclic AMP1–3, acting via protein kinase A4–6, has been identified as the second messenger for several neurotran-smitters, and recent studies have suggested that activation of protein kinase C may have similar modulatory actions on neurones7–11. Calcium and potassium currents have so far been shown to be the major ionic conductances modified by kinase activation4–11. We now report that hippocampal pyramidal cells contain a previously undescribed voltage-dependent chloride current which is active at resting potential and is turned off either by membrane depolarization or by activation of protein kinase C by phorbol esters. We propose that this current may reside predominantly in the cell's dendritic membrane and thereby may regulate dendritic excitability.