# Carbonic anhydrase inhibitors are specific openers of skeletal muscle BK channel of K+-deficient rats.
> カリウム欠乏ラット骨格筋BKチャネルに対する炭酸脱水酵素阻害薬の選択的開口作用


## Abstract

Six carbonic anhydrase (CA) inhibitors were evaluated for their effects on Ca²⁺-activated K⁺ (BK) channels in skeletal muscle of potassium-deficient rats, an animal model of hypokalemic periodic paralysis. Patch-clamp recordings from excised membrane patches showed that acetazolamide (ACTZ, DE50=7.3×10⁻⁶ M), bendroflumethiazide (BFT, DE50=5.93×10⁻⁵ M), etoxzolamide (ETX, DE50=1.17×10⁻⁴ M), and dichlorphenamide (DCP) each activated BK channels, whereas methazolamide and hydrochlorothiazide did not. Molecular modeling revealed that BK channel-opening capacity correlated with two structural features: an intramolecular hydrogen bond with inter-atomic distances of 1.82–3.01 Å and an electron-poor aromatic ring. These pharmacophoric elements were present in the active compounds but absent in the inactive ones. The findings indicate that BK channel activation is a direct property of certain CA inhibitors, mediated through interaction with channel subunits and independent of CA enzyme inhibition.

### Mechanism

Certain CA inhibitors possess an intramolecular hydrogen bond (1.82–3.01 Å inter-atomic distance) and an electron-poor aromatic ring that interact directly with BK channel subunits, opening the channel independently of CA enzyme inhibition.

## Bibliographic

- **Authors**: Tricarico D, Barbieri M, Mele A, Carbonara G, Camerino DC
- **Journal**: FASEB J
- **Year**: 2004
- **PMID**: [14766795](https://pubmed.ncbi.nlm.nih.gov/14766795/)
- **DOI**: [10.1096/fj.03-0722fje](https://doi.org/10.1096/fj.03-0722fje)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: not assessed

## Delivery context

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 14766795. https://h2-papers.org/en/papers/14766795
> **Source**: PubMed PMID [14766795](https://pubmed.ncbi.nlm.nih.gov/14766795/)