Abstracts

Rationale: Temporal lobe epilepsy (TLE) is a common form of adult epilepsy involving the limbic structures of the temporal lobe. Layer II neurons of the entorhinal cortex (EC) form the major excitatory input into the hippocampus via the perforant path and consist of non-stellate and stellate neurons. These neurons are spared and hyper-excitable in TLE. Since sodium (Na) channels play a critical role in action potential (AP) generation and conduction we sought to determine if Na channel gating parameters and expression levels were altered in TLE. Specifically we focused on persistent (INaP) and resurgent (INaR) Na currents since these two currents arise mainly from activation of the Nav1.6 Na channel isoform and are major contributors to the generation of AP bursts. Methods: Brain slices were prepared from control rats and rats with TLE. INaP and INaR currents were recorded from visually identified EC layer II non-stellate and stellate neurons. Results: Both TLE stellate and non-stellate neurons had larger INaP current amplitudes when compared to control neurons. In non-stellate neurons control INaP currents had an amplitude of -121.3 26.1 pA (n = 9) and were significantly (P<0.01) increased in TLE to -358 46.2 pA (n = 7). In a similar manner, TLE stellate neurons also had increased INaP current amplitudes. Amplitudes were increased from -153.5 18.9 pA (n = 9) under control conditions to -356.8 31.7 pA (n = 7: P < 0.01) in TLE. INaR current amplitudes were also increased in TLE. INaR currents in non-stellate neurons were profoundly increased from -514.8 72.4 pA (n = 6) in control to -1394.6 82.1 pA (n = 7: P < 0.001) in TLE. INaR currents in stellate neurons were also significantly larger in TLE compared to controls. Control amplitudes were increased from -568.9 58.9 pA (n = 7) to -1477.8 75.2 pA (n = 7: P < 0.001) in TLE. Families of INaR currents were evoked to construct current voltage plots. TLE non-stellate neurons had significantly (P<0.05) hyperpolarized INaR V1/2 values (-61.3 1.9; n=7 in control compared with -68.0 2.3; n=8 in TLE). Slopes were also slowed in TLE (-5.0 0.6 in control compared with -6.2 0.5 in TLE). In contrast to non-stellate neurons, INaR V1/2 values in stellate neurons were unchanged (-70.1 2.8; n=10: in control compared with -65.4 2.9; n=6 in TLE). Slope values were slowed in TLE (-4.0 0.4 in control compared with -7.0 0.4 in TLE; P<0.05). Immunohistochemistry experiments revealed increased staining intensity of Nav1.6 along the axon initial segment (AIS) in TLE brain slices when compared to control.