Inactivation gate

Figure 8. A schematic for the toxin binding sites on the voltage-gated Na channel. Toxin-free open and closed conformations are drawn at the left and center. Separate sites are depicted within the membrane for activators such as BTX, VTD (A), and brevetoxin (B) these are coupled to each other and to the a-peptide toxin site (a), which is kinetically linked to the -peptide toxin site (P see ref. 20). Near the outer opening of the pore is a site (G) for STX and TTX which is affected by binding at site A and which can modify inactivation gating.

Fig. 5. Proposed topology of K channel subunits inserted into the membrane. COO carboxy-terminal. The proposed membrane-spanning segments SI-S6 in the core region of channel proteins are displayed linearly. H5 may be part of the K channel pore. The amino-terminal inactivation gate is symbolized by a positively charged ball which could occlude the pore region. The extracellular side is thought to be at top and the intracellular side at bottom.

Voltage-dependent activation requires moving charges 105 The fast inactivation gate is on the inside 106... 

This protein is fixed in the cell membrane, and is sensitive to voltage. When the cell is sufficiently depo adzed, a conformational change occurs in the protein, allowing flow of Na+ across the membrane. After several milliseconds, an inactivation gate closes, ceasing the flux of Na+. The inactivation gate is likely located on an intracellular loop between domains III and IV. 

Fig. 1. Example of a receptor structure. Some anti-epileptic drugs interact with a receptor site on a Na" " channel and enhance the activity of the inactivation gate (I) decreasing the ahihty of neurons to fire at high frequencies. (A) indicates the activation gate of this ion channel. (Reprinted by permission from McNamara JO. Emerging insights into the genesis of epilepsy. Nature 1999 399(Suppl) A15-22, 1999 Macmillan Magazines Ltd.)...

A schematic representation of Na+ channels cycling through different conformational states during the cardiac action potential. Transitions between resting, activated, and inactivated states are dependent on membrane potential and time. The activation gate is shown as m and the inactivation gate as h. Potentials typical for each state are shown under each channel schematic as a function of time. The dashed line indicates that part of the action potential during which most Na+ channels are completely or partially inactivated and unavailable for reactivation. 

Patton, D. E., Isom, L. L., Catterall, W. A., Goldin, A. L. The adult rat brain pi subunit modifies activation and inactivation gating of multiple sodium channel a subunits, J Biol Chem 1994, 269, 17649-17655. 

The molecular mechanism of local anesthesia, the location of the local anesthetic dibucaine in model membranes, and the interaction of dibucaine with a Na+-channel inactivation gate peptide have been studied in detail by 2H- and 1H-NMR spectroscopy [24]. Model membranes consisted of PC, PS, and PE. Dibucaine was deuterated at H9 and H3 of the butoxy group and at the 3-position of the quinoline ring. 2H-NMR spectra of the multilamellar dispersions of the lipid mixtures were obtained. In addition, spectra of deuterated palmitic acids incorporated into mixtures containing cholesterol were obtained and the order parameter, SCD, for each carbon... 

Fig. 5.5 A hinged-lid model for Na+-channel inactivation and schematic representation of the interaction between a local anesthetic drug and the amino acid residues in the inactivation gate. (Reprinted from Fig. 2 of ref.

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