AI Article Synopsis
- Lolitrem B is a neurotoxin linked to ryegrass staggers, causing symptoms like tremors and lack of coordination in animals.
- It inhibits large conductance calcium-activated potassium (BK) channels at very low concentrations and has been shown to specifically impact motor functions through these channels.
- The study investigated various lolitrem compounds to determine structural features critical for their effectiveness as BK channel inhibitors, identifying seven new inhibitors and two key structural elements essential for high potency.
Article Abstract
Lolitrem B is an indole-diterpenoid neurotoxin which is the main causative agent of ryegrass staggers, an animal disease associated with tremors and incoordination. It is also a potent inhibitor of large conductance calcium-activated potassium (BK) channel activity (IC(50)=4 nM). Furthermore, we have recently shown that the motor function deficits induced by lolitrem B are specifically mediated by BK channels, making the toxin a valuable tool for investigating the molecular function and physiological roles of these channels. To determine what structural features of BK channel agents are required for high potency, the effect of lolitrem B and seven structurally-related lolitrems on BK channel activity has been measured. Concentration-responses and conductance-voltage (G-V) relationships were determined for each compound and related to the different structure types. This study has identified seven new BK channel inhibitors and has allowed the identification of two key structural features required for high potency BK channel activity by lolitrems.
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| http://dx.doi.org/10.1016/j.ejphar.2008.12.031 | DOI Listing |
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