Functions of the Persistent Naþ Current in Cortical Neurons Revealed by Dynamic Clamp

Many cortical neurons and other vertebrate nerve cells are equipped with a persistent Na current, INaP, which operates at membrane potentials near the action potential threshold. This current may strongly influence integration and transduction of synaptic input into spike patterns. However, due to the lack of pharmacological tools for selective blockade or enhancement of INaP, its impact on spike generation has remained enigmatic. By using dynamic clamp to cancel or add INaP during intracellular recordings in rat hippocampal pyramidal cells, we were able to circumvent this long-standing problem. Combined with computational modeling our dynamic-clamp experiments disclosed how INaP strongly affects the transduction of excitatory current into action potentials in these neurons. First, we used computational model simulations to predict functional roles of INaP, including unexpected effects on spike timing and current–frequency relations. We then used the dynamic-clamp technique to experimentally test and confirm our model predictions.