Chung-Chin Kuo

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Phenytoin, carbamazepine, and lamotrigine are anticonvulsants frequently prescribed in seizure clinics. These drugs all show voltage-dependent inhibition of Na+ currents, which has been implicated as the major mechanism underlying the antiepileptic effect. In this study, I examine the inhibition of Na+ currents by mixtures of different anticonvulsants.(More)
1. Lamotrigine (LTG), a new antiepileptic drug, requires long depolarizations to inhibit Na+ currents. This suggests either slow binding of LTG to the fast inactivated state or selective binding of LTG to the slow inactivated state of Na+ channels. To differentiate between these possibilities and to characterize further the action of LTG, we studied the(More)
Carbamazepine and phenytoin, two of the most commonly prescribed antiepileptic drugs, have been proposed to share a similar mechanism of action by use-dependent inhibition of Na+ channels. The proposed similar mechanism of action, however, cannot explain the common clinical experiences that the two drugs are different; in some patients, one drug may be more(More)
Rapidly inactivating K+ current (KA current) is recorded from rat hippocampal neurons by whole-cell patch-clamp technique and suitable voltage protocols. It is found that imipramine, a commonly prescribed tricyclic antidepressant, is an open KA channel blocker with a binding rate constant of 5.6 x 10(6) M-1 s-1 and an apparent dissociation constant of no(More)
The NMDA receptor opens in response to binding of NMDA and glycine. However, it remains unclear where and how gating of the NMDA receptor pore is accomplished. We show that different point mutations between S645 and I655 (thus including the highly conserved SYTANLAAF motif) of M3c in NR2B lead to constitutively open channels. The current through these(More)
An increase in neuronal burst activities in the subthalamic nucleus (STN) is a well-documented electrophysiological feature of Parkinson disease (PD). However, the causal relationship between subthalamic bursts and PD symptoms and the ionic mechanisms underlying the bursts remain to be established. Here, we have shown that T-type Ca(2+) channels are(More)
Tetrodotoxin-resistant (TTX-R) Na channels are 1,000-fold less sensitive to TTX than TTX-sensitive (TTX-S) Na channels. On the other hand, TTX-R channels are much more susceptible to external Cd 2 block than TTX-S channels. A cysteine (or serine) residue situated just next to the aspartate residue of the presumable selectivity filter “DEKA” ring of the(More)
Diphenhydramine is an H1 histamine receptor antagonist, yet it also has a clinically useful local anesthetic effect. We found that diphenhydramine inhibits the neuronal Na(+) current, and the inhibition is stronger with more positive holding potentials. The dissociation constant between diphenhydramine and the inactivated Na(+) channel is approximately 10(More)
BACKGROUND Despite the structural differences, local anesthetics, anticonvulsants, and tricyclic antidepressants exert similar use-dependent actions against voltage-gated Na channels, which may be contributory to pain control. The authors explore whether these drugs could doubly occupy the channel and exert synergic clinical effect. METHODS The authors(More)
Use-dependent block of Na(+) channels plays an important role in the action of many medications, including the anticonvulsants phenytoin, carbamazepine, and lamotrigine. These anticonvulsants all slowly yet selectively bind to a common receptor site in inactivated but not resting Na(+) channels, constituting the molecular basis of the use-dependent block.(More)