How cesium dialysis affects the passive properties of pyramidal neurons: Implications for voltage clamp studies of persistent sodium current

In order to accurately understand and model neuronal integration in the brain, we must know the biophysical properties of channels that are located far from, the soma, in the axonal and dendritic membranes of central nerve cells. Reliable electrophysiological measurements in these regions are difficult to obtain, because the processes are too tiny to directly study with an electrode. One common strategy is to record with a somatic electrode that contains Cs ⁺, to dialyze the intracellular space with this K⁺ channel blocker, and thereby to render the neuron electrotonically compact. Does this work? Here, we combine the experimental and modeling techniques to determine the extent to which a whole-cell voltage clamp, established with a Cs ⁺-containing pipette in the soma of a cortical pyramidal cell, attains adequate voltage control of distal neuronal processes. We focus on the low-voltage-activated, slowly inactivating 'persistent' Na⁺ current (I_NaP), that plays a crucial role in determining neuronal excitability and synaptic integration.