Abstracts

Rationale: Similar to neurons, cardiomyocytes exhibit activity-dependent remodeling mediated through the activation of intracellular signaling cascades. Cardiac remodeling has been observed following pilocarpine-induced status epilepticus (SE) model of acquired epilepsy including resting tachycardia, increased sympathetic tone and altered ion channel expression. However, the onset and the signaling cascades that contribute to the cardiac remodeling in epilepsy remain to be examined. Ca²⁺/calmodulin-dependent protein kinase II (CamKII) and p42/44 mitogen activated protein kinase (ERK1/2) pathways are 2 major signaling cascades underlying the activity-dependent remodeling in primary cardiac pathology. CamKII modulates Ca²⁺cycling during excitation-contraction coupling and plays a role in tachyarrhythmias. ERK1/2 activation has been observed following stimulation of the adrenergic receptors and contributes to cardiac hypertrophy. Therefore, these kinase pathways represent candidate signaling cascades involved in cardiac remodeling in epilepsy. Methods: We used kainate (18mg/kg, i.p.) to induce SE in the juvenile male rats (150-200g). The rats remained in SE for 1 h, followed by pentobarbital administration (20mg/kg, i.p.) to stop the seizures. At 2 wks following SE, we obtained single channel EKG recordings from the SE and the age-matched sham rats (n=14-18/group). Heart rate (HR), PR, QRS and QTc intervals were manually calculated. In a subset of the animals (n=4/group), we examined the phosphorylation of CamKII at T286 and ERK1/2 at T202/Y204. The intensity of the protein bands was semi-quantified using Image J software. We analyzed the data using Student t-test. The results are expressed as mean±SEM. Results: Compared with the sham rats, the SE rats exhibited increased HR (319±11 vs. 282±5 bpm, p<0.01), prolonged QRS (8.2±0.4 vs. 6.6±0.6 ms, p<0.05) and QTc intervals (306.7±9.7 vs. 253.7±11 ms, p<0.01) at 2 wks following SE. The SE rats also exhibited increased phosphorylated CamKII (303.0±52.30% vs.100±40.98%, p<0.01) and ERK1/2 levels (202±12.8% vs. 100±9.7%,