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Characterization of a fast transient outward current in neocortical neurons from epilepsy patients

✍ Scribed by C. Rüschenschmidt; R. Köhling; M. Schwarz; H. Straub; A. Gorji; E. Siep; A. Ebner; H.W. Pannek; I. Tuxhorn; P. Wolf; E.-J. Speckmann


Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
332 KB
Volume
75
Category
Article
ISSN
0360-4012

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✦ Synopsis


Abstract

A‐type currents powerfully modulate discharge behavior and have been described in a large number of different species and cell types. However, data on A‐type currents in human brain tissue are scarce. Here we have examined the properties of a fast transient outward current in acutely dissociated human neocortical neurons from the temporal lobe of epilepsy patients by using the whole‐cell voltage‐clamp technique. The A‐type current was isolated with a subtraction protocol. In addition, delayed potassium currents were reduced pharmacologically with 10 mM tetraethylammonium chloride. The current displayed an activation threshold of about −70 mV. The voltage‐dependent activation was fitted with a Boltzmann function, with a half‐maximal conductance at −14.8 ± 1.8 mV (n = 5) and a slope factor of 17.0 ± 0.5 mV (n = 5). The voltage of half‐maximal steady‐state inactivation was −98.9 ± 8.3 mV (n = 5), with a slope factor of −6.6 ± 1.9 mV (n = 5). Recovery from inactivation could be fitted monoexponentially with a time constant of 18.2 ± 7.5 msec (n = 5). At a command potential of +30 mV, application of 5 mM 4‐aminopyridine or 100 μM flecainide resulted in a reduction of A‐type current amplitude by 35% or 22%, respectively. In addition, flecainide markedly accelerated inactivation. Current amplitude was reduced by 31% with application of 500 μM cadmium. All drug effects were reversible. In conclusion, neocortical neurons from epilepsy patients express an A‐type current with properties similar to those described for animal tissues. © 2004 Wiley‐Liss, Inc.


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