Channel specificity, voltage gating

Some channels are voltage gated, so that they open or close at a specific membrane potential to aid in neurotransmission. 

Schultz, J., Hoffmuller, U., Krause, G., Ashurst, J., Macias, M. J., Schmieder, P., Schneider-Mergener, J., and Oschknat, H. (1998). Specific interactions between the syntrophin PDZ domain and voltage-gated sodium channels. Nat. Struct. Biol. 5, 19-24. 

Figure 5.1 Mechanism of action at a chemical synapse. The arrival of an action potential at the axon terminal causes voltage-gated Ca++ channels to open. The resulting increase in concentration of Ca++ ions in the intracellular fluid facilitates exocytosis of the neurotransmitter into the synaptic cleft. Binding of the neurotransmitter to its specific receptor on the postsynaptic neuron alters the permeability of the membrane to one or more ions, thus causing a change in the membrane potential and generation of a graded potential in this neuron.

Calcium channels have been shown to play a role in epilepsy as well [23]. Currently used antiepileptic drugs exhibit a wide spectrum of activity, including modulation of voltage-gated sodium and calcium channels. T-type calcium channels have been demonstrated to play an important role in absence epilepsy, a specific form of epilepsy characterized by brief lapses in consciousness correlated with spike-and-wave discharges in the electroencephalogram [14,24-28]. Ethosuximide 1 has been shown to block T-type calcium channels and is used clinically to treat absence epilepsy [25]. Several selective small-molecule T-type calcium channel antagonists have demonstrated efficacy in rodent epilepsy models (vide infra). 

Collectively, the in situ biochemical evidence suggests that voltage-gated calcium channels are modified by pyrethroids however, the mechanism by which Types I and II pyrethroids accomplish this may be different. Specifically, Type II pyrethroids are more potent enhancers of calcium influx and glutamate release under depolarizing conditions than Type I pyrethroids and may contribute, in part, to different symptoms elicited by these classes of pyrethroids in vivo. 

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