page_title: Depolarizing prepulse
section_title: Voltage-gated sodium channel
hierarchical_section_title: Depolarizing prepulse / Biophysical mechanisms / Voltage-gated sodium channel
context_page_description: A depolarizing prepulse is an electrical stimulus that causes the potential difference measured across a neuronal membrane to become more positive or less negative, and precedes another electrical stimulus. DPPs may be of either the voltage or current stimulus variety and have been used to inhibit neural activity, selectively excite neurons, and increase the pain threshold associated with electrocutaneous stimulation.
context_section_description: Since the Hodgkin–Huxley model was first proposed in the 1950s, much has been learned concerning the structure and functionality of voltage-gated sodium channels.  Although the exact three dimensional structure of the sodium channel remains unknown, its composition and the functionality of individual components have been determined. Voltage-gated sodium channels are large, multimeric complexes, composed of a single α subunit and one or more β subunits, an illustration of which may be observed in the adjacent image.  The α subunit folds into four homologous domains, each of which contain six α-helical transmembrane segments.  The S₄ segments of each domain serve as voltage sensors for activation.  Each S₄ segment consists of a repeating structure of one positively charged residue and two hydrophobic residues, and these combine to form a helical arrangement.  When the channel is depolarized these S₄ segments undergo a conformational change that widens the helical arrangement and opens the sodium-channel pore.  Within milliseconds after the pore's opening, the intracellular loop that connects domains III and IV, binds to the channel's intracellular pore, inactivating the channel.  Thus, by providing a depolarizing prepulse before a stimulus, there is a greater probability that the inactivating domains of the sodium channels have bound to their respective pores, reducing the stimulus induced sodium influx and the influence of the stimulus.
caption: Diagram of a voltage-sensitive sodium channel α-subunit. G - glycosylation, P - phosphorylation, S - ion selectivity, I - inactivation, positive (+) charges in S4 are important for transmembrane voltage sensing.