Voltagegated Calcium Channels

The voltage-gated calcium channels (VGCCs) are essential in regulating Ca2+ signaling, which is associated with many important cellular events such as the release of excitatory glutamate neurotransmitters, the plasticity changes

Figure 14.1 • Binding of phenytoin to the hypothetical "inactivation gate" receptor on the voltage-gated sodium channels.

of long-term potentiation in learning and memory, and the maintenance of homeostasis of nerve cells. It has been suggested that excessive influx of Ca2+ plays a critical role in the induction and progression of epileptic seizures.22,23 There are distinct classes of VGCCs. The high-threshold L-type Ca2+ channels in the presynaptic glutaminergic receptors require strong depolarization for activation and are the primary molecular targets of gabapentin and prega-balin, both of which are effective in refractory partial seizures.22,24 On the other hand, the low-threshold T-type Ca2+ channels require only weak depolarization for activation and are the molecular targets of AEDs such as etho-suximide and zonisamide.18,25

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