Reduction of human neocortical and guinea pig CA1-neuron A-type currents by organic calcium channel blockers.
In epilepsy models, organic calcium antagonists regularly induce a transient activity increase before suppression of epileptiform discharges. This action was speculated to be mediated by a modulation of potassium currents. Since A-type currents potently regulate neuronal excitability, their modulation by calcium channel blockers was investigated in acutely isolated human neocortical temporal lobe neurons and CA1 neurons of guinea pigs using the whole-cell voltage-clamp technique. In human neurons, 40 microM nifedipine caused an amplitude reduction by 28% at a command potential of -6 mV and produced a biexponential, markedly accelerated current inactivation with time constants of 8.4 +/- 1.1 ms (n = 6) and 62.9 +/- 6.4 ms (n = 5). The time constant under control conditions was 50.1 +/- 8.5 ms (n = 6). Verapamil (40 microM) did not affect the current amplitude, but accelerated the monoexponential current inactivation from 40.2 +/- 7.1 ms to 13.3 +/- 0.8 ms (n = 9). Accordingly, verapamil accelerated the inactivation from 42.3 +/- 5.9 ms to 15.0 +/- 1.3 ms (n = 11) in guinea pig CA1 neurons, without affecting the current amplitude. In this preparation, it was shown that the two enantiomers of verapamil do not differ in their actions. The results show that the A-type current in human neocortical and in guinea pig hippocampal neurons is reduced by organic calcium channel blockers.
Rüschenschmidt
Christiane
C
Institut für Physiologie, Universität Bonn, Robert-Koch-Str. 27a, Bonn, Germany. Christiane.Rueschenschmidt@ukb.uni-bonn.de
Straub
Heidrun
H
Köhling
Rüdiger
R
Siep
Elke
E
Gorji
Ali
A
Speckmann
Erwin-Josef
EJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002648:Child; D004827:Epilepsy / Q000503:physiopathology / Q000601:surgery; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000166:cytology* / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017966:Pyramidal Cells / Q000502:physiology; D013237:Stereoisomerism; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D014700:Verapamil; D009543:Nifedipine