Region-specific upregulation of the hyperpolarization-activated cationic current Ih in the pilocarpine model of epilepsy

H-currents (Ih) play an important role in the regulation of neuronal excitability, being involved in the regulation of resting membrane potential, pacemaking activity and dendritic computation. Here, we investigated whether this current is altered in hippocampal neurons of pilocarpine-treated rats.

The whole-cell voltage-clamp technique was used to study Ih in CA1 pyramidal neurons and dentate gyrus granule cells of pilocarpine-treated and control rats. Ih was elicited by 2s hyperpolarizing voltage steps from a holding potential of –63 mV.

In CA1 neurons, total current amplitudes, current amplitudes normalized to the cell capacitances as well as conductance curves did not differ between control and epileptic animals. Current densities were 1.7±0.1 pA/pF (n=19) and 1.7±0.2 pA/pF (n=16), respectively.

In granule cells, however, we observed an increase of Ih amplitudes and current densities. This increase was more pronounced early after the pilocarpine-treatment before rats developed spontaneous seizures. At this time (7 to 9 days after status epilepticus), current densities were 0.045±0.005 pA/pF (n=15) in control and 0.113±0.013 pA/pF (n=13) in pilocarpine-treated rats (p<0.001). In chronically epileptic animals (35 to 63 days after status epilepticus), current density was 0.081±0.009 pA/pF (n=17) compared with 0.048±0.006 pA/pF (n=18) in controls (p=0.003).

In summary, we describe a region-specific upregulation of Ih in hippocampal granule cells of pilocarpine-treated rats.