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Insulin modulation of ATP-sensitive K+ channel of rat skeletal muscle is impaired in the hypokalaemic state
No full textIn the present work, we examined the effects of in vivo administration of insulin to rats made hypokalaemic by feeding a K+-free diet. The i.p. injection of insulin in the hypokalaemic rats provoked muscle paralysis within 3-5 h. Consistent with this observation, the skeletal muscle fibres of the paralysed rats were depolarized. In contrast, in the normokalaemic animals, insulin neither provoked paralysis nor produced significant fibre hyperpolarization. In the hypokalaemic rats, insulin almost completely abolished the sarcolemma adenosine triphosphate (ATP)-sensitive K+ currents without altering the sensitivity of the channels to ATP or glibenclamide. In contrast, in the normokalaemic rats, insulin enhanced ATP-sensitive K+ currents that became also resistant to ATP and glibenclamide. Our experiments indicate that the modulation of the sarcolemma ATP-sensitive K+ channels by insulin is impaired in the hypokalaemic state. This phenomenon appears to be related to the fibre depolarization and paralysis observed in the same animals
Involvement of K(Ca2+)channels in the local abnormalities and hyperkalemia following the ischemia-reperfusion injury of rat skeletal muscle
No full textPatch-clamp technique was used to investigate the proper-ties of the muscular Ca2+-activated K+ channel (KCa2+) in the ischemic and ischemic-reperfused rat muscle fibers and the possible involvement of this ion channel in the reperfusion-dependent hyperkalemic state. The properties of the muscular KCa2+ channel were unaltered following 4 h of ischemia of the lower limbs and that the serum K+ level did not change following ischemia. In contrast, after 3 h of reperfusion an over-activation of KCa2+ channel was observed which was related to the increase in the number of functional channels per patch area. Currents from cation aselective channels were also routinely detected in these muscles and ion channel abnormalities similar to those observed in the ischemic-reperfused muscles were also found in the contralateral muscles. Significant hyperkalemia was observed following 3 h of reperfusion. Administration of L-NAME (10 mg.kg(-1)), a nitric-oxide synthase (NOS) inhibitor, during reperfusion prevented the increase of KCa2+ channel activity and the activation of the cation aselective channel. The L-NAME treatment also partially antagonised the characteristic hyperkalemia observed following reperfusion. In contrast, D-NAME (20 mg.kg(-1)), the inactive antipode on NOS enzyme administered to the rats during reperfusion failed to prevent the overactivation of the KCa2+ channel or the hyperkalemia. Our results indicate that overactivation of KCa2+ channel found in the muscles following reperfusion is either directly or indirectly related to NOS activation, and contributes to the hyperkalemia. Moreover, the discovery of abnormalities similar to those of the ischemic-reperfused muscles in the contralaterals suggests that proinflammatory molecules were released from the ischemic area, accentuating the pathological state
Figg. 2 a-b, 4, 8, 12 in M. LIVADIOTTI - G. ROCCO, La Curia del Foro Vecchio di Leptis Magna: risultati preliminari di un nuovo studio architettonico, in L'Africa Romana - XIX Convegno Internazionale di Studi Trasformazione dei paesaggi del potere nell’Africa settentrionale fino alla fine del mondo antico, Sassari-Alghero, 16-19 dicembre 2010, Roma 2012, pp. 325-344
No full textCorrelazione tra parametri chimico-fisici e presenza di Legionella spp nella rete idrica
No full textFigg. 2 a, b, 3, 4, 5 in M. LIVADIOTTI,La Curia del Foro Vecchio di Leptis Magna: un caso poco noto di anastilosi parziale, in Restauri dell’antico. Ricerche ed esperienze nel Mediterraneo greco. Selinunte, 20-25 ottobre 2011, ROMA: L'Erma di Bretschneider
No full textThe biophysical and pharmacological characteristics of skeletal muscle ATP-sensitive K+ channels are modified in K+-depleted rat, an animal model of hypokalemic periodic paralysis.Mol Pharmacol
No full textWe evaluated the involvement of the sarcolemmal ATP-sensitive
K1 channel in the depolarization of skeletal muscle fibers
occurring in an animal model of human hypokalemic periodic
paralysis, the K1-depleted rat. After 23–36 days of treatment
with a K1-free diet, an hypokalemia was observed in the rats.
No difference in the fasting insulinemia and glycemia was found
between normokalemic and hypokalemic rats. The fibers of the
hypokalemic rats were depolarized. In these fibers, the current
of sarcolemmal ATP-sensitive K1 channels measured by the
patch-clamp technique was abnormally reduced. Cromakalim,
a K1 channel opener, enhanced the current and repolarized the
fibers. At channel level, two open conductance states blocked
by ATP and stimulated by cromakalim were found in the hypokalemic
rats. The two states could be distinguished on the
basis of their slope conductance and open probability and were
never detected on muscle fibers of normokalemic rats. It is
known that insulin in humans affected by hypokalemic periodic
paralysis leads to fiber depolarization and provokes paralysis.
We therefore examined the effects of insulin at macroscopic
and single-channel level on hypokalemic rats. In normokalemic
animals, insulin applied in vitro to the muscles induced a glybenclamide-
sensitive hyperpolarization of the fibers and also
stimulated the sarcolemmal ATP-sensitive K1 channels. In contrast,
in hypokalemic rats, insulin caused a pronounced fiber
depolarization and reduced the residual currents. Our data
indicated that in hypokalemic rats, an abnormally low activity of
ATP-sensitive K1 channel is responsible for the fiber depolarization
that is aggravated by insulin
Modulation of K+ channel activity of striated fibers of hypokalemic rats underlies the therapeutical efficacy of minoxidil and acetazolamide.
No full textTu-Pos390
MODULATION OF K+ CHANNEL ACTIVITY OF STRIATED FIBERS OF
HYPOKALEMIC RATS UNDERLIES THE THERAPEUTICAL EFFICACY OF
MINOXIDIL AND ACETAZOLAMIDE. ((D. Tricaiico, M. Barbieri, R. Mallamaci , R.
Capriulo* and D. Conte Camerino)) Dept. of Pharnacobiology, Faculty of Pharmacy and
*Clinic of Aniestesiology and Intensive Care, Faculty of Medicine, University of Bari, ITALY.
K' depleted rats (hypoK rats) resemble humans affected by hypokalemic periodic paralysis for
the serum K+ levels lower than 3.2meq/L, the muscle fiber depolarization and the attacks of
paralysis induced by acute injection of insulsn (4U/IOOgr) and/or glucose (0.5gr) (Lehmann-
Hom et al., Myology: 1303-1310,1994). Moreover, skeletal muscle fibers of hypoK rats have an
abnormally lower activity of ATP sensitive K' channels (KATp) (Tricarico et al., Biophys.J.
72/2:A249, 1997). We observed by patch clamp recordings, that in vitro application of
minoxidil sulphate increased KATP activity of normokalemic rat striated fibers
(ED55=465±4pM) and significantly restored KATP currents of hypoK rats fibers
(ED50=11±2gM). Accordingly, minoxidil sulphate (1-100lM) repolarized hypoK rats fibers,
effect antagonized by glybenclamide (60-lO0nM). To evaluate the potential benefit of in vivo
administration of minoxsdil to hypoK rats, 8 depleted animals were treated for 10 days with
18jg/kg/die minoxidil. The effects were compared with those of 2.8mg/kg/die acetazolamide (4
hypoK rats), a drug currently used in the therapy of human hypokalemic periodic paralysis.
Acetazolamide restored normal serum K' levels, whereas minoxidil did not. However, 50% of
the rats treated with either minoxidil or acetazolamide were not paralyzed after the acute
injection of insulin and glucose. In vitro recordings on muscle fibers from no-paralyzed treated
rats showed normal values of resting potential and further hyperpolarization in low K' solution.
This effect was antagonized by glybenclamide in minoxidil treated and by charybdotoxin in the
acetazolamide treated rat fibers. Furthermore, patch clamp recordings showed that the
treatment with minoxidil restored the KATP channel activity whereas acetazolamide increased
Ca2+activated K+ channel activity. These results suggest that KATP channel openers could be
beneficial in the therapy of hypokalemic periodic paralysis and increase our understanding on
the mechanism of action of acetazolamide. (Telethon Italy project n°579)
The biophysical and pharmacological characteristics of skeletal muscle ATP-Sensitive K+ channels are modified in K+-depleted rat, an animal model of hypokalemic periodic paralysis
No full textWe evaluated the involvement of the sarcolemmal ATP-sensitive K+ channel in the depolarization of skeletal muscle fibers occurring in an animal model of human hypokalemic periodic paralysis, the K+-depleted rat. After 23-36 days of treatment with a K+-free diet, an hypokalemia was observed in the rats. No difference in the fasting insulinemia and glycemia was found between normokalemic and hypokalemic rats. The fibers of the hypokalemic rats were depolarized. In these fibers, the current of sarcolemmal ATP-sensitive K+ channels measured by the patch-clamp technique was abnormally reduced. Cromakalim, a K+ channel opener, enhanced the current and repolarized the fibers. At channel level, two open conductance states blocked by ATP and stimulated by cromakalim were found in the hypokalemic rats, The two states could be distinguished on the basis of their slope conductance and open probability and were never detected on muscle fibers of normokalemic rats. It is known that insulin in humans affected by hypokalemic periodic paralysis leads to fiber depolarization and provokes paralysis. We therefore examined the effects of insulin at macroscopic and single-channel level on hypokalemic rats. In normokalemic animals, insulin applied in vitro to the muscles induced a glybenclamide-sensitive hyperpolarization of the fibers and also stimulated the sarcolemmal ATP-sensitive K+ channels. In contrast, in hypokalemic rats, insulin caused a pronounced fiber depolarization and reduced the residual currents. Our data indicated that in hypokalemic rats, an abnormally low activity of ATP-sensitive K+ channel is responsible for the fiber depolarization that is aggravated by insulin
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