Isopimaric acid

Isopimaric acid (IPA) is a toxin which acts as a large conductance Ca2+-activated K+ channel (BK channel) opener.

Chemistry
IPA is one of the members of the resin acid group and it is a tricyclic diterpene.

Target
IPA acts on the large-conductance calcium activated K+ channels (BK channels).

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). 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.