Carbonic-anhydrase inhibitors are effective in channelopathies possibly by opening the Ca2C-activated-KCchannels. However, the in vivo effects of these drugs in KC-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 inKC-deficient rats treated in vivo with dichlorphenamide (DCP), ethoxzolamide (ETX), hydrochlorthiazide (HCT), methazolamide (MTZ), bendroflumethiazide (BFT) and acetazolamide (ACTZ). Ten days treatments ofKC-deficient rats with DCP, BFT, ETX and ACTZ (5.6 mg/kg per day) restored the serum [KC] to control values and prevented the insulin-induced paralysis. In ex vivo experiments, the carbonic-anhydrase inhibitors enhanced the activity of Ca2C-activated-KCchannels with the order of efficacy: ACTZOBFTOETXODCP. In contrast, HCT and MTZ failed to stimulate the Ca2C-activated-KCchannels and to prevent the hypokalaemia and paralysis. At the concentration of 1 mg/kg per day, all these drugs failed to ameliorate the hypokalaemic-PP symptoms. The activation of Ca2C-activated-KCchannel in addition to the mild diuretic effect explained the efficacy of ACTZ and DCP in KC-deficient rats and in familial hypokalaemic-PP.
Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels
TRICARICO, Domenico;MELE A;CONTE, Diana
2006-01-01
Abstract
Carbonic-anhydrase inhibitors are effective in channelopathies possibly by opening the Ca2C-activated-KCchannels. However, the in vivo effects of these drugs in KC-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 inKC-deficient rats treated in vivo with dichlorphenamide (DCP), ethoxzolamide (ETX), hydrochlorthiazide (HCT), methazolamide (MTZ), bendroflumethiazide (BFT) and acetazolamide (ACTZ). Ten days treatments ofKC-deficient rats with DCP, BFT, ETX and ACTZ (5.6 mg/kg per day) restored the serum [KC] to control values and prevented the insulin-induced paralysis. In ex vivo experiments, the carbonic-anhydrase inhibitors enhanced the activity of Ca2C-activated-KCchannels with the order of efficacy: ACTZOBFTOETXODCP. In contrast, HCT and MTZ failed to stimulate the Ca2C-activated-KCchannels and to prevent the hypokalaemia and paralysis. At the concentration of 1 mg/kg per day, all these drugs failed to ameliorate the hypokalaemic-PP symptoms. The activation of Ca2C-activated-KCchannel in addition to the mild diuretic effect explained the efficacy of ACTZ and DCP in KC-deficient rats and in familial hypokalaemic-PP.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
