Hyperpolarization-activated cation currents in human epileptogenic neocortex

Authors: Wierschke, Stephan; Lehmann, Thomas-Nicolas¹; Dehnicke, Christoph²; Horn, Peter¹; Nitsch, Robert³; Deisz, Rudolf A.³

Source: Epilepsia, Volume 51, Number 3, March 2010 , pp. 404-414(11)

Publisher: Wiley-Blackwell

Abstract:

Summary Purpose: 

Hyperpolarization-activated cation currents (I_H) play a pivotal role in the control of neuronal excitability. In animal models of epilepsy both increases and decreases of I_H have been reported. We, therefore, characterized properties of I_H in human epileptogenic neocortex. Methods: 

Layer II/III neurons in slices from epilepsy surgery tissues and rat cortex were investigated with whole-cell patch-clamp recordings. Results: 

A total of 484 neurons from 96 temporal lobe epilepsy (TLE) tissues and 32 neurons from 8 frontal lobe epilepsy (FLE) tissues were recorded. Voltage-clamp recordings revealed on hyperpolarizing command steps two time- and voltage-dependent inward currents, namely a fast, Ba²⁺-sensitive current (K_IR) and a slowly activating current, namely consisting of two kinetically distinct components sensitive to the established I_H blocker ZD7288. Only, the fast component (I_H(fast)) of TLE neurons was on average smaller and activated more slowly (density 2.7 ± 1.6 pA/pF; tau 38.4 ± 34.0 ms) than in FLE neurons (4.7 ± 2.3 pA/pF; 16.6 ± 7.9 ms; p < 0.001 for both). Within the TLE tissues the I_H(fast) density (averaged per patient) was smaller in cases with numerous annual grand mal seizures (GM; 2.2 ± 0.6 pA/pF) compared to those with few GM (2.8 ± 1.0 pA/pF; p = 0.0184). A similar difference was obtained in the case of complex partial seizures (CPS; many CPS 2.2 ± 0.6 pA/pF; few CPS 2.9 ± 1.0 pA/pF, p = 0.0037). Discussion: 

The biophysical properties of I_H in cortices from TLE, FLE, and rat tissue suggest a deficit of HCN1 subunits in the human epileptogenic neocortex, which in turn may increase excitability and probability of seizure activity.

Keywords: Epilepsy; HCN channels; Patch-clamp; Pharmacoresistance; Temporal lobe

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1528-1167.2009.02275.x

Affiliations: 1: Department of Neurosurgery, Charité Universitätsmedizin Berlin, Berlin, Germany 2: Epilepsie-Zentrum Berlin-Brandenburg, Koenigin-Elisabeth-Krankenhaus Herzberge, Berlin, Germany 3: Institute for Cell Biology and Neurobiology, Center for Anatomy, Charité Universitätsmedizin Berlin, Berlin, Germany

Publication date: 2010-03-01

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