Editing Aconitine (section)

==Mechanism of action==
Aconitine can interact with the voltage-dependent [[sodium channel|sodium-ion channels]], which are proteins in the cell membranes of excitable tissues, such as cardiac and skeletal muscles and [[neuron]]s. These proteins are highly selective for sodium ions. They open very quickly to [[depolarization|depolarize]] the cell membrane potential, causing the upstroke of an action potential. Normally, the sodium channels close very rapidly, but the depolarization of the membrane potential causes the opening (activation) of potassium channels and potassium efflux, which results in repolarization of the membrane potential.

Aconitine binds to the channel at the neurotoxin binding site&nbsp;2 on the alpha subunit (the same site bound by [[batrachotoxin]], [[veratridine]], and [[grayanotoxin]]).<ref>{{cite journal | vauthors = Gutser UT, Friese J, Heubach JF, Matthiesen T, Selve N, Wilffert B, Gleitz J | title = Mode of antinociceptive and toxic action of alkaloids of Aconitum spec | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 357 | issue = 1 | pages = 39–48 | date = January 1998 | pmid = 9459571 | doi = 10.1007/pl00005136 | s2cid = 21509335 }}</ref> This binding results in a sodium-ion channel that stays open longer. Aconitine suppresses the conformational change in the sodium-ion channel from the active state to the inactive state. The membrane stays depolarized due to the constant sodium influx (which is 10–1000-fold greater than the potassium efflux). As a result, the membrane cannot be repolarized. The binding of aconitine to the channel also leads to the channel to change conformation from the inactive state to the active state at a more negative voltage.<ref>{{cite journal | vauthors = Benoit E | title = Mécanisme(s) d'action des neurotoxines agissant sur l'inactivation des canaux sodium activés par le potentiel de membrane |trans-title=Mechanism of action of neurotoxins acting on the inactivation of voltage-gated sodium channels | language = fr | journal = Comptes Rendus des Séances de la Société de Biologie et de Ses Filiales | volume = 192 | issue = 3 | pages = 409–436 | year = 1998 | pmid = 9759381 }}</ref> In neurons, aconitine increases the permeability of the membrane for sodium ions, resulting in a huge sodium influx in the axon terminal. As a result, the membrane depolarizes rapidly. Due to the strong depolarization, the [[Cell membrane#Permeability|permeability]] of the membrane for potassium ions increases rapidly, resulting in a potassium reflux to release the positive charge out of the cell. Not only the permeability for potassium ions but also the permeability for calcium ions increases as a result of the depolarization of the membrane. A calcium influx takes place. The increase of the calcium concentration in the cell stimulates the release of the [[Acetylcholine receptor|neurotransmitter acetylcholine]] into the [[Chemical synapse|synaptic cleft]]. [[Acetylcholine]] binds to acetylcholine receptors at the postsynaptic membrane to open the sodium-channels there, generating a new action potential.

Research with mouse nerve-hemidiaphragm muscle preparation indicate that at low concentrations (<0.1&nbsp;μM) aconitine increases the electrically evoked acetylcholine release causing an induced muscle tension.<ref>{{cite journal | vauthors = Okazaki M, Kimura I, Kimura M | title = Aconitine-induced increase and decrease of acetylcholine release in the mouse phrenic nerve-hemidiaphragm muscle preparation | journal = Japanese Journal of Pharmacology | volume = 66 | issue = 4 | pages = 421–426 | date = December 1994 | pmid = 7723217 | doi = 10.1254/jjp.66.421 | url = http://www.jstage.jst.go.jp/article/jphs1951/66/4/66_4_421/_pdf | format = pdf | doi-access = free }}</ref> Action potentials are generated more often at this concentration. At higher concentration (0.3–3&nbsp;μM) aconitine decreases the electrically evoked acetylcholine release, resulting in a decrease in muscle tension. At high concentration (0.3–3&nbsp;μM), the sodium-ion channels are constantly activated, transmission of action potentials is suppressed, leading to non-excitable target cells or paralysis.