| Title | Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels. | | Author(s) | Tricarico D, Mele A, Conte Camerino D | | Institution | Unit of Pharmacology, Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, via Orabona no. 4,70126 Bari, Italy. | | Source | Neuromuscul Disord 2006 Jan; 16(1):39-45. | | MeSH | Adenosine Triphosphate
Animals
Calcium
Carbonic Anhydrase Inhibitors
Comparative Study
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Interactions
Electric Stimulation
Hypokalemic Periodic Paralysis
Male
Membrane Potentials
Muscles
Patch-Clamp Techniques
Potassium Channels, Calcium-Activated
Potassium Deficiency
Rats
Rats, Wistar
Research Support, Non-U.S. Gov't
Spectrophotometry
| | Abstract | Carbonic-anhydrase inhibitors are effective in channelopathies possibly by opening the Ca2+-activated-K+ channels. However, the in vivo effects of these drugs in K+-deficient rats, the animal model of familial hypokalaemic periodic paralysis(hypokalaemic-PP), are currently unknown. Measures of insulin-responses, serum electrolytes levels and patch-clamp experiments were therefore performed in K+ -deficient rats treated in vivo with dichlorphenamide (DCP), ethoxzolamide (ETX), hydrochlorthiazide (HCT), methazolamide (MTZ), bendroflumethiazide (BFT) and acetazolamide (ACTZ). Ten days treatments of K+-deficient rats with DCP, BFT, ETX and ACTZ (5.6 mg/kg per day) restored the serum [K+] to control values and prevented the insulin-induced paralysis. In ex vivo experiments, the carbonic-anhydrase inhibitors enhanced the activity of Ca2+-activated-K+ channels with the order of efficacy: ACTZ>BFT>ETX>DCP. In contrast, HCT and MTZ failed to stimulate the Ca2+-activated-K+ channels and to prevent the hypokalaemia and paralysis. At the concentration of 1mg/kg per day, all these drugs failed to ameliorate the hypokalaemic-PP symptoms. The activation of Ca2+-activated-K+ channel in addition to the mild diuretic effect explained the efficacy of ACTZ and DCP in K+ -deficient rats and in familial hypokalaemic-PP. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 16368240 |
|
