Gating mechanisms sodium channels

Catterall WA (2000) From ionic currents to molecular mechanisms the structure and function of voltage-gated sodium channels. Neuron 26 13-25... 

The primary mechanism of action of local anesthetics is blockade of voltage-gated sodium channels (Figure 26-2). 

LAs block nerve conduction when applied locally to nervous tissue by a voltage- and frequency-dependent inhibition of sodium currents (see Voltage-gated Sodium Channels Structure and Function1). Due to this mechanism, they preferentially block hyperexcitable cells and interfere comparatively less with normal physiological sensory and motor function. However, they are not selective for pain-relevant sodium channel subtypes so that they have a relatively high risk of adverse effects associated with the central nervous and cardiovascular systems when administered systemically. Known LAs are not active when administered orally. 

Bennett, E., Urcan, M., Tinkle, S., Koszowski, A., Levinson, S. Contribution of sialic acid to the voltage dependence of sodium channel gating. A possible electrostatic mechanism, J. Gen. Physiol. 

Catterall WA. Molecular mechanisms of gating and drug block of sodium channels. Novartis Found Symp. 2002 241 206-218. 

Cestele S, Catterall WA (2000) Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 82 883-892... 

Carbamazepine is both an important anticonvulsant in therapeutic doses and a powerful proconvulsant in overdose. The therapeutic anticonvulsant mechanism is primarily related to blockade of presynaptic voltage-gated sodium channels. Blockade of the sodium channels is believed to inhibit the release of synaptic glutamate and possibly other neurotransmitters. Carbamazepine is also a powerful inhibitor of the muscurinic and nicotinic acetylcholine receptors, N-methyl-D-aspartate (NMDA) receptors and the central nervous system (CNS) adenosine receptors. In addition, carbamazepine is structurally related to the cyclic antidepressant impramine and in massive overdose may affect cardiac sodium channels. 

Molecular mechanisms of gating and drug block of sodium channels... 

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