1,720,983 research outputs found
Cysteine restores the activity of ATP-sensitive potassium channels of skeletal muscle fibers of aged rats
No full textExpression of electrical and contractile properties of rat skeletal muscle during development: effect of early pharmacological block of chloride channel conductance
No full text
Effects of new K+ channel openers (2H-[1, 4]-benzoxazin-3-one derivatives) on skeletal muscle K-ATP channel.
No full textBiophysical changes of skeletal muscle K-ATP channels in K+ depleted rats and pharmacological interventions.
No full textW-Pos2
BIOPHYSICAL CHANGES OF SKELETAL MUSCLE KATP CHANNELS IN Kl DEPLETED RATS AND
PHAIRMAOLOGICAL INTERVENTION'S
((D. Tricarico. R. Mallamaci. V. Tortorella* and D. Conte Camerino)) Dept. of
Pharmacobiology, and Dept. of Medicinal Chlsmisqn*. Faculty of Pharmacy. Universitv of
Bari, Bari, ITALY.
Recently, mutations in the gene encoding the al-subunit of the skeletal muscle Ca2'channel
have been found in patients affected by hypokalemic periodic paralysis (HOPP) (Sipos et al..
J.Phvsiol. 483.2-299, 1995). However, the link between the fiber depolarization, the paralysis
and the Ca2+ channel mutation is still obscure. The administration of ATP sensitive K'
channels (KATp) openers, pinacidil and cromakalim, to HOPP patients prevents the muscle
paralysis. In the present work we investigated the properties of KATP channels of skeletal
muscle fibers of K' depleted rats (Hypo K'), the animal model of HOPP. In these rats, we
tested cromakalim, and vanadate and me.xiletine, drugs that have been shown to open KATP
channels of cardiac cells. A treatment of male Wistar rats with K' free diet for 38-45 days led
to a drop of serum K' level from 5.0+0.1 meq/L in the normokalemic rats (normo K-) to
2.6+0.2 meq/L in the Hypo K' rats. In these animals, the resting potential of the extensor
digitorum longus (EDL) muscle fibers of the Hypo K+ rats, recorded by the two microelectrode
technique. was drastically reduced. Further depolarization occurred after "in vivo" and "in
vitro" administration of insulin. Similar phenomenas occurs in HOPP patients. Patch clamp
recordings, showed that the mean current of KATP channel was reduced in the Hypo K' rats.
Two types of KATP channels have been found in the Hypo K+ rats. The first type, had a low
single channel conductance (y) of 29+4 pS. Whereas, y was 71+1 pS in the normo K' rats.
The second type had a KATP channel with normal y but an altered selectivity to K' ion. Both
types of channels partially lost the sensitivity to both MgATP and MgADP. Cromakalim (10-
100 FM), vanadate (500 FLM) and mexiletine (100-500 ,uM) restored the KATP conductance and
prevented the fiber depolarization induced by insulin in Hypo K+ rats. Our data indicate that
closure of KATP channels contributes to the fiber depolarization in the Hypo K+ rats. and that
this animal model is suitable to search for therapeutic strategies in HOPP. (Telethon-Italy.
project n° 579)
Different sulfonylurea and ATP sensitivity characterizes the juvenile and the adult form of K-ATP channel complex of rat skeletal muscle
No full textWe have described here the changes of the biophysical and pharmacological properties of the sarcolemmel ATP-sensitive K+ channels (K-ATP) of rat skeletal muscle fibres, occurring from an early postnatal period (5 days) to adulthood (210 days). The age-dependent changes of the mean current of the K-ATP channel (channel activity) and the effects of the blockers, ATP and glybenclamide, were examined by using the patch-clamp technique. Measurements of the single channel conductance, open probability and channel density were also performed. Excision of cell-attached patches into an ATP-free solution dramatically increased the K-ATP channel activity; however, the intensity of this activity was age dependent. The relative activity was low at 5-6 days of postnatal life, increased to a plateau at 12-13 days, then declined toward adult values after 37 days. Two distinct types of the K-ATP channel complex could be distinguished. The early developmental period (5-6 days) was dominated by a K-ATP channel having a conductance of 66 pS, a high open probability of 0.602, and an IC50 for ATP and glybenclamide of 123.1 mu M and 3.97 mu M respectively. This type of channel disappeared with maturation of the muscle to be replaced by the adult form of the K-ATP channel. The latter developmental period (from 56 days) was dominated by a K-ATP channel having a 71 pS conductance, but a low open probability of 0.222. This adult channel was also 3.2 and 73.5 times more sensitive to ATP and glybenclamide, respectively. We have also observed that the sensitivity of the K-ATP channel to ATP and glybenclamide develops differently. Indeed, the greater increase in the sensitivity of the channel to ATP was observed between 5 and 12 days of age. Conversely, the greater enhancement of the sensitivity of the channel to glybenclamide occurred between 12 and 37 days. A further increase of this parameter was also observed between 37 and 56 days of age. The differential age-dependent acquisition of the sensitivity of K-ATP channels to ATP and glybenclamide poses the hypothesis that in rat skeletal muscle the ATP regulatory site and sulfonylurea site are located on different subunits of the K-ATP channel complex. The intense K-ATP channel activity recorded between 12 and 37 days of postnatal life sustains the high resting macroscopic K+ conductance characteristic of the early postnatal development
Actin sliding velocity on pure myosin isoforms from hindlimb unloaded mice
No full textAIM:
Notwithstanding the widely accepted idea that following disuse skeletal muscles become faster, an increase in shortening velocity was previously observed mostly in fibres containing type 1 myosin, whereas a decrease was generally found in fibres containing type 2B myosin. In this study, unloaded shortening velocity of pure type 1 and 2B fibres from hindlimb unloaded mice was determined and a decrease in type 2B fibres was found.
METHODS:
To clarify whether the decrease in shortening velocity could depend on alterations of myosin motor function, an in vitro motility assay approach was applied to study pure type 1 and pure type 2B myosin from hindlimb unloaded mice. The latter approach, assessing actin sliding velocity on isolated myosin in the absence of other myofibrillar proteins, enabled to directly investigate myosin motor function.
RESULTS:
Actin sliding velocity was significantly lower on type 2B myosin following unloading (2.70 ± 0.32 μm s(-1) ) than in control conditions (4.11 ± 0.35 μm s(-1) ), whereas actin sliding velocity of type 1 myosin was not different following unloading (0.89 ± 0.04 μm s(-1) ) compared with control conditions (0.84 ± 0.17 μm s(-1) ). Myosin light chain (MLC) isoform composition of type 2B myosin from hindlimb unloaded and control mice was not different. No oxidation of either type 1 or 2B myosin was observed. Higher phosphorylation of regulatory MLC in type 2B myosin after unloading was found.
CONCLUSION:
Results suggest that the observed lower shortening velocity of type 2B fibres following unloading could be related to slowing of acto-myosin kinetics in the presence of MLC phosphorylation
Metabolically regulated K+ channels of human skeletal muscle fibres in different pathophysiological situations
No full textCalcium activated K+ channel as a target of prompt-to-use drugs in neuromuscular disorders
No full text
- …
