INaP underlies intrinsic spiking and rhythm generation in networks of cultured rat spinal cord neurons

Authors


Dr P. Darbon, as above.
E-mail: darbon@pyl.unibe.ch

Abstract

We have shown previously that rhythm generation in disinhibited spinal networks is based on intrinsic spiking, network recruitment and a network refractory period following the bursts. This refractory period is based mainly on electrogenic Na/K pump activity. In the present work, we have investigated the role of the persistent sodium current (INaP) in the generation of bursting using patch-clamp and multielectrode array recordings. We detected INaP exclusively in the intrinsic spiking cells. The blockade of INaP by riluzole suppressed the bursting by silencing the intrinsic spiking cells and suppressing network recruitment. The blockade of the persistent sodium current produced a hyperpolarization of the membrane potential of the intrinsic spiking cells, but had no effect on non-spiking cells. We also investigated the involvement of the hyperpolarization-activated cationic current (Ih) in the rhythmic activity. The bath application of ZD7288, a specific Ih antagonist, slowed down the rate of the bursts by increasing the interburst intervals. Ih was present in ∼ 70% of the cells, both in the intrinsic spiking cells as well as in the non-spiking cells. We also found both kinds of cells in which Ih was not detected. In summary, in disinhibited spinal cord cultures, a persistent sodium current underlies intrinsic spiking, which, via recurrent excitation, generates the bursting activity. The hyperpolarization-activated cationic current contributes to intrinsic spiking and modulates the burst frequency.

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