Functions of the Persistent Na+ Current in Cortical Neurons Revealed by Dynamic Clamp
Many cortical neurons and other vertebrate nerve cells are equipped with a persistent Na+ current, I NaP, 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 I NaP, its impact on spike generation has remained enigmatic. By using dynamic clamp to cancel or add I NaP 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 I NaP strongly affects the transduction of excitatory current into action potentials in these neurons. First, we used computational model simulations to predict functional roles of I NaP, 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.
KeywordsPyramidal Neuron Axon Initial Segment Repetitive Firing Spike Threshold Subthreshold Oscillation
Our work was supported by the Norwegian Research Council (NFR) through FUGE, NevroNor, and the Norwegian Centre of Excellence programs, and by HFSP for Research Grant RGP0049 to L.J.G. and J.F.S.
- Borg-Graham L (1987). Modelling the somatic electrical behavior of hippocampal pyramidal neuron. Massachusetts Institute of Technology. Ref Type: Thesis/DissertationGoogle Scholar
- Hu H, Vervaeke K, & Storm JF (2002). Two forms of electrical resonance at theta frequencies, generated by M-current, h-current and persistent Na+ current in rat hippocampal pyramidal cells. J Physiol 545, 783–805.Google Scholar
- Mattson RH, Cramer JA, Collins JF, Smith DB, gado-Escueta AV, Browne TR, Williamson PD, Treiman DM, McNamara JO, & McCutchen CB (1985). Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 313, 145–151.PubMedCrossRefGoogle Scholar