Upregulation of a T-type Ca2+ channel causes a long-lasting modification of neuronal firing mode after status epilepticus.

A single episode of status epilepticus (SE) causes numerous structural and functional changes in the brain that can lead to the development of a chronic epileptic condition. Most studies of this plasticity have focused on changes in excitatory and inhibitory synaptic properties. However, the intrinsic firing properties that shape the output of the neuron to a given synaptic input may also be persistently affected by SE. Thus, 54% of CA1 pyramidal cells, which normally fire in a regular mode, are persistently converted to a bursting mode after an episode of SE induced by the convulsant pilocarpine. In this model, intrinsic bursts evoked by threshold-straddling depolarizations, and their underlying spike afterdepolarizations (ADPs), were resistant to antagonists of N-, P/Q-, or L-type Ca2+ channels but were readily suppressed by low (30-100 microm) concentrations of Ni2+ known to block T- and R-type Ca2+ channels. The density of T-type Ca2+ currents, but not of other pharmacologically isolated Ca2+ current types, was upregulated in CA1 pyramidal neurons after SE. The augmented T-type currents were sensitive to Ni2+ in the same concentration range that blocked the novel intrinsic bursting in these neurons (IC50 = 27 microm). These data suggest that SE may persistently convert regular firing cells to intrinsic bursters by selectively increasing the density of a Ni2+-sensitive T-type Ca2+ current. This nonsynaptic plasticity considerably amplifies the output of CA1 pyramidal neurons to synaptic inputs and most probably contributes to the development and expression of an epileptic condition after SE.