Characterization of a fast transient outward current in neocortical neurons from epilepsy patients.
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 microM 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 microM 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.
Institut für Physiologie, Westfälische Wilhelms-Universität, Münster, Germany. christiane.rueschenschmidt@ukb.uni-bonn.de
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Rüschenschmidt
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Köhling
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Schwarz
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Straub
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Gorji
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Siep
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Ebner
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Pannek
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Tuxhorn
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Wolf
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Speckmann
D000293:Adolescent; D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002675:Child, Preschool; D004827:Epilepsy / Q000503:physiopathology*; D005260:Female; D005424:Flecainide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D019579:Neocortex / Q000473:pathology*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D002104:Cadmium; D013779:Tetrodotoxin; D019789:Tetraethylammonium; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D005424:Flecainide