Abstract
Tetrodotoxin (TTX) is a highly specific blocker of voltage-gated sodium channels. The dissociation constant of block varies with different channel isoforms. Until recently, channel resistance was thought to be primarily imparted by amino acid substitutions at a single position in domain I. Recent work reveals a novel site for tetrodotoxin resistance in the P-region of domain IV.
Highlights
Voltage-gated sodium channels (Nav) are membrane-bound proteins that initiate action potentials in nerve and muscle cells and are critical elements of proper function in these tissues [1]
Sodium channels are formed by a 260 kDa α-subunit that is associated with one β subunit (β1) in skeletal muscle cells and with two β subunits (β3 and β1 or β2) in the central nervous system [2]
When the positively charged residues in the fourth membrane-spanning segment (S4) transmembrane regions are replaced with uncharged amino acids, the voltage-dependence of channel gating is altered as would be expected in the region of the channel that acts as a voltage sensor [9, 10]
Summary
Voltage-gated sodium channels (Nav) are membrane-bound proteins that initiate action potentials in nerve and muscle cells and are critical elements of proper function in these tissues [1]. Drugs 2006, 4 sodium ions through the membrane This step, along with the activation of voltage-gated potassium channels, allows the membrane to repolarize and ends the action potential. After channels open in response to membrane depolarization, they rapidly inactivate which stops the flow of sodium ions into the cell. This form of channel gating occurs when the linker between the third and fourth domains of the channel physically occludes the intracellular mouth of the channel pore [9, 13,14,15,16]. The extent to which these regions interact is a subject of ongoing study
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