Isopimaric acid (IPA) is a

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

which acts as a large conductance Ca²⁺-activated K⁺ channel (

BK channel BK channels (big potassium), are large conductance calcium-activated potassium channels, also known as Maxi-K, slo1, or Kca1.1. BK channels are voltage-gated potassium channels that conduct large amounts of potassium ions (K+) across the ce ...

) opener.

Sources

IPA originates from many sorts of trees, especially conifers.

Chemistry

IPA is one of the members of the

resin acid Resin acid refers to mixtures of several related carboxylic acids, primarily abietic acid, found in tree resins. Nearly all resin acids have the same basic skeleton: three fused rings having the empirical formula C19H29COOH. Resin acids are tacky, ...

group and it is a tricyclic diterpene.

Target

IPA acts on the large-conductance calcium activated K+ channels (

s).

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 Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion '' Leiurus quinquestriatus hebraeus'' (''deathstalker'') that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous syst ...

(CTX). Opening of the BK channel leads to an increased K⁺-efflux which hyperpolarizes the

resting membrane potential A relatively static membrane potential which is usually referred to as the ground value for trans-membrane voltage. The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as oppo ...

, reducing the excitability of the cell in which the BK-channel is expressed.

Toxicity

Studies on rainbow

trout Trout are species of freshwater fish belonging to the genera '' Oncorhynchus'', ''Salmo'' and ''Salvelinus'', all of the subfamily Salmoninae of the family Salmonidae. The word ''trout'' is also used as part of the name of some non-salmoni ...

hepatocytes have shown that IPA increases intracellular

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

release, leading to a disturbance in the calcium homeostasis. This could be important in the possible toxicity of the toxin.

Notes

References

* * {{Ion channel modulators Ion channel toxins Carboxylic acids Diterpenes Non-protein ion channel toxins Potassium channel openers Phenanthrenes Vinyl compounds