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Inhibitory Effect of Lamotrigine on A‐type Potassium Current in Hippocampal Neuron–Derived H19‐7 Cells
Author(s) -
Huang ChinWei,
Huang ChaoChing,
Liu YenChin,
Wu ShengNan
Publication year - 2004
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.0013-9580.2004.58403.x
Subject(s) - lamotrigine , chemistry , inhibitory postsynaptic potential , tetraethylammonium , quinidine , tetraethylammonium chloride , patch clamp , potassium channel blocker , hippocampal formation , pharmacology , biophysics , membrane potential , 4 aminopyridine , potassium channel , potassium , neuroscience , medicine , biochemistry , epilepsy , biology , receptor , organic chemistry
Summary: Purpose: We investigated the effects of lamotrigine (LTG) on the rapidly inactivating A‐type K + current ( I A ) in embryonal hippocampal neurons. Methods: The whole‐cell configuration of the patch‐clamp technique was applied to investigate the ion currents in cultured hippocampal neuron–derived H19‐7 cells in the presence of LTG. Effects of various related compounds on I A in H19‐7 cells were compared. Results: LTG (30 μ M –3 m M ) caused a reversible reduction in the amplitude of I A . The median inhibitory concentration (IC 50 ) value required for the inhibition of I A by LTG was 160 μ M . 4‐Aminopyridine (1 m M ), quinidine (30 μ M ), and capsaicin (30 μ M ) were effective in suppressing the amplitude of I A , whereas tetraethylammonium chloride (1 m M ) and gabapentin (100 μ M ) had no effect on it. The time course for the inactivation of I A was changed to the biexponential process during cell exposure to LTG (100 μ M ). LTG (300 μ M ) could shift the steady‐state inactivation of I A to a more negative membrane potential by approximately −10 mV, although it had no effect on the slope of the inactivation curve. Moreover, LTG (100 μ M ) produced a significant prolongation in the recovery of I A inactivation. Therefore in addition to the inhibition of voltage‐dependent Na + channels, LTG could interact with the A‐type K + channels to suppress the amplitude of I A . The blockade of I A by LTG does not simply reduce current magnitude, but alters current kinetics, suggesting a state‐dependent blockade. LTG might have a higher affinity to the inactivated state than to the resting state of the I A channel. Conclusions: This study suggests that in hippocampal neurons, during exposure to LTG, the LTG‐mediated inhibition of these K + channels could be one of the ionic mechanisms underlying the increased neuronal excitability.