Effects of the Ih blockers CsCl and ZD7288 on inherited epilepsy in Mongolian gerbils.

The h current (Ih) is an inwardly mixed cationic conductance activated by membrane hyperpolarization. We previously demonstrated that the Ih blockers CsCl and ZD7288 can significantly increase the threshold of electrically induced paroxysmal discharge in the rabbit hippocampus. In the present study, we examined the effects of these Ih blockers on inherited epilepsy in Mongolian gerbils. Seizure-sensitive Mongolian gerbils (n=29) underwent a series of seizure induction tests (including gentle handling for 1-2 min and being dropped from a height of 50 cm) before, during and after oral administration of 10 mM CsCl or 0.1 mM ZD7288. Their behavioral responses were classified into 3 grades corresponding to no seizure (score: 0), partial seizure (score: 1), and generalized seizure (score: 2). In the CsCl experiments (n=10), the average scores were 1.09 +/- 0.10 before administration, 0.82 +/- 0.10 during administration, and 0.96 +/- 0.10 after administration. CsCl significantly increased the ratio of grade 0 behavioral responses (P<0.01, compared with the value before administration), and decreased the ratio of grade 1 responses (P<0.01). In the ZD7288 experiments (n=19), the average scores were 0.99 +/- 0.07 before administration, 0.52 +/- 0.06 (P<0.01) during administration, and 0.76 +/- 0.07 (P<0.05) after administration. ZD7288 significantly increased the ratio of grade 0 behavioral responses (P<0.01), and decreased the ratio of grade 1 responses (P<0.05) and grade 2 responses (P<0.01). We conclude that both CsCl and ZD7288 have an anti-epileptic effect on inherited epilepsy in Mongolian gerbils.