Isopimaric acid explained
Isopimaric acid (IPA) is a toxin which acts as a large conductance Ca2+-activated K+ channel (BK channel) opener.
Sources
IPA originates from many sorts of trees, especially conifers.[1]
Chemistry
IPA is one of the members of the resin acid group and it is a tricyclic diterpene.[1]
Target
IPA acts on the large-conductance calcium activated K+ channels (BK channels).[2] [3]
Mode of action
BK channels are formed by α subunits and accessory β subunits arranged in tetramers. The α subunit forms the ion conduction pore and the β subunit contributes to channel gating. IPA interaction with the BK channel enhances Ca2+ and / or voltage sensitivity of the α subunit of BK channels without affecting the channel conductance. In this state BK channels can still be inhibited by one of their inhibitors, like charybdotoxin (CTX).[2] [3] Opening of the BK channel leads to an increased K+-efflux which hyperpolarizes the resting membrane potential, reducing the excitability of the cell in which the BK-channel is expressed.
Toxicity
Studies on rainbow trout hepatocytes have shown that IPA increases intracellular calcium release, leading to a disturbance in the calcium homeostasis. This could be important in the possible toxicity of the toxin.
See also
References
- 10.1016/S0166-445X(98)00115-5 . The resin acids dehydroabietic acid and isopimaric acid release calcium from intracellular stores in rainbow trout hepatocytes . 1999 . Råbergh . Christina M.I. . Lilius . Henrik . Eriksson . John E. . Isomaa . Boris . Aquatic Toxicology . 46 . 55–65.
- 10.1016/0166-445X(92)90050-W . The resin acids dehydroabietic acid and isopimaric acid inhibit bile acid uptake and perturb potassium transport in isolated hepatocvtes from rainbow trout (Oncorhynchus mykiss) . 1992 . Råbergh . C.M.I. . Isomaa . B. . Eriksson . J.E. . Aquatic Toxicology . 23 . 3–4 . 169–179.
Notes and References
- 8795202 . 1996 . Wilson . AE . Moore . ER . Mohn . WW . Isolation and characterization of isopimaric acid-degrading bacteria from a sequencing batch reactor . 62 . 9 . 3146–51 . 168108 . Applied and Environmental Microbiology. 10.1128/aem.62.9.3146-3151.1996 . 1996ApEnM..62.3146W .
- 8807400 . 1996 . Kaczorowski . GJ . Knaus . HG . Leonard . RJ . McManus . OB . Garcia . ML . High-conductance calcium-activated potassium channels; structure, pharmacology, and function . 28 . 3 . 255–67 . Journal of Bioenergetics and Biomembranes . 10.1007/bf02110699. 25857254 .
- 12237330 . 2002 . Imaizumi . Y . Sakamoto . K . Yamada . A . Hotta . A . Ohya . S . Muraki . K . Uchiyama . M . Ohwada . T . Molecular basis of pimarane compounds as novel activators of large-conductance Ca(2+)-activated K(+) channel alpha-subunit . 62 . 4 . 836–46 . Molecular Pharmacology . 10.1124/mol.62.4.836.