Sodium gating mechanisms

Smith, J.J. and Blumenthal, K.M. (2007) Site-3 anemone toxins molecular probes of gating mechanisms in voltage-dependent sodium channels. Toxicon, 49,159-170. 

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

However, it was not until over a century later that the underlying mechanism was explained in terms of the properties of the specific membrane proteins forming the voltage-gated ion channels of sodium and potassium ions. 

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

Scholtz A Mechanisms of (local) anaesthetics on voltage-gated sodium and other ion channels. Br J Anaesth 2002 89 52. 

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. 

Preparation of sodium Urushi/ISFET. A mixture of 5 wt. % of ETH 227, 45 wt. % of di-2-ethylhexylphthalate (DOP Kishida Chemical Co. Ltd.) containing 0.5 wt. % of potassium tetrakis(4-chlorophenyl)borate (Dojin Research Laboratories Co. Ltd.) and 50 wt. % of Urushi (Saito Urushi Co. Ltd.) was coated on the FET devices and then the resulting Na+ Urushi membranes were hardened for 10 days at 30 °C and 90% relative humidity. The thickness of the membrane was approximately 0.1 mm. The surface of the Urushi matrix membrane was lustrous, smooth and adhesive to the gate of the device. The hardening mechanisms were discussed in detail elsewhere (6). 

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

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