Abstract
The persistent Na$^+$ current, INaP, is known to amplify subthreshold
oscillations and synaptic potentials, but its impact on action potential
generation remains enigmatic. Using computational modeling, whole-cell
recording, and dynamic clamp of CA1 hippocampal pyramidal cells in
brain slices, we examined how INaP changes the transduction of excitatory
current into action potentials. Model simulations predicted that
INaP increases afterhyperpolarizations, and, although it increases
excitability by reducing rheobase, INaP also reduces the gain in
discharge frequency in response to depolarizing current (f/I gain).
These predictions were experimentally confirmed by using dynamic
clamp, thus circumventing the longstanding problem that INaP cannot
be selectively blocked. Furthermore, we found that INaP increased
firing regularity in response to sustained depolarization, although
it decreased spike time precision in response to single evoked EPSPs.
Finally, model simulations demonstrated that I(NaP) increased the
relative refractory period and decreased interspike-interval variability
under conditions resembling an active network in vivo.
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