Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels.

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.

• Authors: Domenico Tricarico, Antonietta Mele, Diana Conte Camerino
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 16 Issue 1 Pg. 39-45 (Jan 2006) ISSN: 0960-8966 [Print] England
• PMID: 16368240 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbonic Anhydrase Inhibitors
• Potassium Channels, Calcium-Activated
• Adenosine Triphosphate
• Calcium

Topics

• Adenosine Triphosphate (pharmacology)
• Animals
• Calcium (pharmacology)
• Carbonic Anhydrase Inhibitors (therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Interactions
• Electric Stimulation (methods)
• Hypokalemic Periodic Paralysis (drug therapy, etiology, metabolism)
• Male
• Membrane Potentials (drug effects, physiology, radiation effects)
• Muscles (drug effects, physiopathology)
• Patch-Clamp Techniques (methods)
• Potassium Channels, Calcium-Activated (drug effects, physiology)
• Potassium Deficiency (complications)
• Rats
• Rats, Wistar
• Spectrophotometry (methods)