1 Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5; and 2 Department of Molecular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The objective of this study was to determine how an ATP-sensitive K+ (KATP) channel deficiency affects the contractile and fatigue characteristics of extensor digitorum longus (EDL) and soleus muscle of 2- to 3-mo-old and 1-yr-old mice. KATP channel-deficient mice were obtained by disrupting the Kir6.2 gene that encodes for the protein forming the pore of the channel. At 2-3 mo of age, the force-frequency curve, the twitch, and the tetanic force of EDL and soleus muscle of KATP channel-deficient mice were not significantly different from those in wild-type mice. However, the tetanic force and maximum rate of force development decreased with aging to a greater extent in EDL and soleus muscle of KATP channel-deficient mice (24-40%) than in muscle of wild-type mice (7-17%). During fatigue, the KATP channel deficiency had no effect on the decrease in tetanic force in EDL and soleus muscle, whereas it caused a significantly greater increase in resting tension when compared with muscle of wild-type mice. The recovery of tetanic force after fatigue was not affected by the deficiency in 2- to 3-mo-old mice, whereas in 1-yr-old mice, force recovery was significantly less in muscle of KATP channel-deficient than wild-type mice. It is suggested that the major function of the KATP channel during fatigue is to reduce the development of a resting tension and not to contribute to the decrease in force. It is also suggested that the KATP channel plays an important role in protecting muscle function in older mice.
Kir6.2; knockout; mouse; twitch; tetanus; force-frequency curve
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
WHEN THE INTRACELLULAR ATP concentration decreases and/or the intracellular ADP, H+, and lactate concentrations increase (14, 18, 23, 28), the ATP-sensitive K+ (KATP) channel, a voltage-insensitive K+ channel, is activated. There is now excellent evidence that the KATP channels of cardiac and skeletal muscle are activated during ischemia, hypoxia, and metabolic inhibition (6, 8, 9). The KATP channel can thus regulate the electrical activity of the cell membrane in relation to the energy state of the cell.
Noma (18) postulated that the function of the KATP channel is to protect muscle against deleterious energy depletion and irreversible function impairment. To accomplish such function, it has been postulated that the KATP channel reduces force development because muscle activity can increase the metabolic rate 20-fold in slow mammalian muscle and up to 500-fold in amphibian muscle (30). The mechanism of action of the KATP channel involves an increase in K+ conductance, which then contributes to a shortening of the action potential duration (8, 9) and to an increase in the extracellular K+ concentration (4, 8). Greater K+ concentration then depolarizes the cell membrane (10), which increases the proportion of inactivated Na+ channels (1). Together, the shortening of action potential and the inactivation of Na+ channels reduce membrane excitability that leads to a decrease in Ca2+ release (3) and force production (8). The Ca2+-ATPase and myosin ATPase then use less energy because there is less Ca2+ and force.
Muscle fatigue is defined as a decrease in the capacity of a muscle to develop force when it is stimulated repetitively. The decrease in force can be as high as 90% (16). It has, therefore, been suggested that the KATP channel plays an important role in the etiology of muscle fatigue. Indeed, an activation of the KATP channel with pinacidil or levcromakalim increases the rate of fatigue (16, 29), which is evidence that the channel can contribute to the decrease in force. However, most studies have reported that blocking the KATP channel with either glibenclamide (1-100 µM) or tolbutamide (2 mM) does not affect the rate of fatigue (5, 7, 15, 26, 29).
Matar et al. (16) recently showed, with the use of mouse
extensor digitorum longus (EDL) and soleus, that 10 µM glibenclamide does not affect the rate of fatigue, but causes large increases in
resting tension, which develops when muscles fail to relax between
contractions. They suggested that the number of activated KATP channels was too small to affect force development
during fatigue. However, the efficiency of glibenclamide to block
KATP channels decreases when the ADP concentration
increases (27). It is, therefore, possible that the lack
of a glibenclamide effect on the rate of fatigue was due to an
incomplete block of the KATP channels. Furthermore,
glibenclamide at 20 µM increases the Ca2+ sensitivity
of the contractile apparatus (7, 16). Although this effect is not observed at 10 µM glibenclamide in unfatigued muscle, it is still possible that this effect occurs in fatigued muscle
fibers. Consequently, the effect of glibenclamide on the resting
tension may be due to a nonspecific effect of glibenclamide, such as
the Ca2+ sensitivity of the contractile components.
Classical KATP channels comprise two subunits, the
pore-forming subunit Kir6.2 and a sulfonylurea receptor (SUR1 or SUR2) (2, 22). Whereas pancreatic -cell KATP
channels comprise Kir6.2 and SUR1 (12), skeletal muscle
comprise Kir6.2 and SUR2A (11, 22). Recently, a
KATP channel-deficient mouse (Kir6.2
/
) was
generated by disrupting the Kir6.2 gene in a C57Bl6/J mouse (defined here as the wild-type or Kir6.2+/+ mouse)
(17). The skeletal muscle of a Kir6.2
/
mouse has no KATP channel activity in its cell membrane
(Seino, unpublished data). Thus the Kir6.2
/
mouse gives
a new approach to the study of the physiological role of the
KATP channel.
The first objective of this study was, therefore, to determine whether a KATP channel deficiency affects the kinetics of fatigue. Matar et al. (16) determined the effects of glibenclamide on the EDL and soleus muscle of 2- to 3-mo-old mice. We therefore used muscle from mice of the same age to compare the effects of the KATP channel deficiency with those of glibenclamide. The second objective of this study was to determine whether a KATP channel deficiency adversely affects muscle function over time. For this, we compared the capacity to generate tetanic force (defined as the maximum force a muscle can develop) and the kinetics of fatigue in EDL and soleus muscle of 2- to 3-mo-old and 1-yr-old mice. The results showed 1) the KATP channel reduces the development of resting tension during fatigue but does not affect the rate of fatigue; and 2) the capacity to generate tetanic force in both EDL and soleus decreases in KATP channel-deficient mice to a greater extent than in wild-type mice when the animals get older.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Animals
Kir6.2+/+ (or wild-type) and Kir6.2Force Measurement
Force measurement was as described by Matar et al. (16). Briefly, mice were anesthetized with an intraperitoneal injection of pentobarbitol sodium (Somnotol) delivered at a dose of 0.8 mg/10 g body wt. EDL and soleus muscle were excised, and both tendons were tied with surgical silk to allow attachment of muscle to the experimental apparatus. Muscles were constantly immersed in physiological saline solution that contained (in mM) 118.5 NaCl, 4.7 KCl, 2.4 CaCl2, 3.1 MgCl2, 25 Na2HCO3, 2 NaH2PO4, and 5.5 D-glucose. The solution was continuously bubbled with 95% O2-5% CO2 and had a pH of 7.4. The temperature of all experiments was 37°C.Muscles were stimulated by passing a current between parallel platinum
wires located on opposite sides of the muscle. Twitch contractions were
elicited with 0.3-ms-long rectangular pulses of 8 V (supramaximal
voltage). Tetanic contractions were elicited with a 200-ms-long train
of pulses at 140 Hz for soleus muscle and 200 Hz for EDL muscle. Force
was measured with a Kulite semiconductor strain gauge (model BG100) and
digitized with a Keithley Metrabyte analog-to-digital board (model
DAS50). Sampling rates were 20 kHz for twitch contractions and 5 kHz
for tetanic contractions. Twitch or tetanic force was defined as the
force that developed during stimulation. It was calculated as the
difference between the maximum force during contraction and the
force (or tension) measured 5 ms before the contraction (see
Fig. 1A for tetanic force). A resting tension developed when muscles failed to fully relax
between contractions during fatigue development. The development of
resting tension was measured as the difference between the tension
measured 5 ms before a contraction and the tension measured 5 ms before
the first contraction of the fatigue period (Fig. 1). Time to peak
during a twitch was calculated as the time interval between the time
5% of the maximum twitch force had developed and the time the maximum
force was reached (this calculation was used to avoid differences
related to the latent period). The half-relaxation time of a twitch was
obtained from the time interval between the time to peak and the time
force had decreased by 50% during relaxation. For the tetanus, the
half-relaxation time was obtained from the time interval between the
last stimulus of a train of pulses and the time force had decreased by
50%. The maximum rate of force development was obtained by measuring
the slope of the force change over time at every 10 data points.
|
Experimental Protocol
Two groups of mice were tested. The first group consisted of six 1-yr-old wild-type and six 1-yr-old Kir6.2Hematoxylin and Eosin Staining
The second EDL and soleus muscle of the same mice used for the contractile measurements were frozen in isopentane precooled in liquid nitrogen. Cross sections, 10 µm thick, were postfixed with 10% Formalin (pH 7.0) before being stained for 10 min in 4.7% (wt/vol) hematoxylin solution that contained 2% (vol/vol) glacial acetic acid. After the excess hematoxylin was washed off in water, cross sections were dipped in acidic 70% (vol/vol) alcohol and then in 0.2% (vol/vol) ammonia solution. Cross sections were counterstained in 4.3% (wt/vol) eosin-phloxine solution dissolved in 70% alcohol followed by a wash in 95% alcohol.Statistical Analysis
ANOVA was used to determine significant differences. Two-way ANOVA were used to determine the significant differences for body and muscle weight, as well as the parameters of the twitch and tetanic contractions. Split-plot ANOVA designs were used for the fatigue measurements because muscles were tested at all levels of time during fatigue and recovery. ANOVA calculations were made using the General Linear Model procedures of the Statistical Analysis Software (SAS Institute, Cary, NC). When a main effect or an interaction was significant, the least significant difference was used to locate the significant differences (24). The word "significant" refers only to a statistical difference (P < 0.05). ![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Weight and Contractile Characteristics
The body and muscle weight (Table 1), maximum force, time to peak, and half-relaxation time of the twitch (Table 2), as well as the force-frequency curve (data not shown) of EDL and soleus muscle of Kir6.2
|
|
|
Significant differences were, however, observed for the parameters of
the tetanic contraction for the 1-yr-old mice. First, the tetanic force
and the maximum rate of force development were significantly less
(24-40%) in the EDL and soleus muscle of 1-yr-old mice than 2- to
3-mo-old Kir6.2/
mice. For the wild-type mice, the
differences between the 2- to 3-mo-old and 1-yr-old groups were smaller
(7-17%) and not significant. Second, the tetanic force and the
maximum rate of force development of the EDL muscle of 1-yr-old
Kir6.2
/
mice were also significantly less
(21-23%) than those from age-matched wild-type mice. Third, the
half-relaxation times of soleus muscle of 1-yr-old
Kir6.2
/
mice were not different from those of 2- to
3-mo-old mice, whereas they were significantly slower for the 1-yr-old
wild-type mice.
Cross sections of three EDL and two soleus muscles from 1-yr-old
wild-type and Kir6.2/
mice were stained with
hematoxylin and eosin. There was no evidence of connective tissue
infiltration or muscle fibers with central nuclei in either group of
mice (data not shown). Thus the greater decrease in tetanic force in
Kir6.2
/
muscle when mice got older was not associated
with any apparent muscle damage.
Kinetics of Fatigue
Tetanic force.
When EDL muscles from 2- to 3-mo-old wild-type mice were stimulated
with one tetanic contraction every second, the tetanic force decreased
to 26.7 and 8.8% of the prefatigue force after 30 and 60 s of
stimulation, respectively (Fig.
2A). Thereafter, the tetanic
force decreased very little and was 6.0% after 180 s of
stimulation. For the EDL muscle, there was no significant difference in
the rate of fatigue between wild-type and Kir6.2/
mice
at both 2-3 mo and 1 yr of age.
|
Resting tension.
During fatigue development, muscles eventually failed to fully relax
between contractions, and that gave rise to an increase in resting
tension. The increase in resting tension was small and not
significantly different from zero in EDL muscle of wild-type mice (Fig.
3A). In EDL muscle of
Kir6.2/
mice, the increase in resting tension occurred
sooner and was significantly larger than in the muscle of wild-type
mice. After 30 s of stimulation, the resting tensions of EDL
muscle of 2- to 3-mo-old and 1-yr-old Kir6.2
/
mice
were, respectively, 5.6 and 8.7% of the prefatigue tetanic force. At
the end of the fatigue period, resting tensions were 8.4-8.8% for
the Kir6.2
/
mice, compared with only 1.6-2.2% for
the wild-type mice.
|
Recovery of tetanic force.
After fatigue, tetanic force increased back toward its
prefatigue levels. For the 2- to 3-mo-old mice, the recovery of tetanic force was not significantly different between wild-type and
Kir6.2/
EDL muscle (data not shown). For the 1-yr-old
group, the recovery of tetanic force was significantly greater in EDL
and soleus muscle of wild-type mice than Kir6.2
/
mice
(Fig. 4). The difference between
wild-type and Kir6.2
/
mice was especially large for
soleus muscle, which was 20.5% after 5 min of recovery and 14.2%
after 30 min.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
It has been hypothesized that the KATP
channel plays an important role in protecting muscle against function
impairment (18). In an attempt to further test this
hypothesis, we compared the contractile and fatigue characteristics of
EDL and soleus muscle between wild-type and Kir6.2/
mice, the latter being KATP channel-deficient mice
(17). Compared with muscles from wild-type mice, we found
that KATP channel-deficient muscles had 1) less
capacity to relax between contractions as they developed greater
resting tension during fatigue; 2) smaller capacity to
recover tetanic force after fatigue (1-yr-old mice only); and
3) greater loss of tetanic force when mice get older.
Comparison of the Effects of Glibenclamide With Those of a KATP Channel Deficiency on the Kinetics of Fatigue
Matar et al. (16) studied the role of the KATP channel during fatigue in EDL and soleus muscle of 2- to 3-mo-old mice with the use of glibenclamide, a KATP channel blocker. As described in the Introduction, the glibenclamide effects can be influenced by its efficiency to block the channels when the ADP concentration increases (27) and by its effect on the Ca2+ sensitivity of the contractile apparatus (7, 16). Although drug specificity and efficiency are not considered when KATP channel-deficient mice are used, these mice can develop compensations that mask the effect of no KATP channel in the cell membrane. To determine whether any compensation, drug specificity, and/or efficiency are important to consider, we can compare the effects of the KATP deficiency from the data from 2- to 3-mo-old mice obtained from this study with those of glibenclamide from Matar et al. (16).First, neither glibenclamide nor a KATP channel deficiency
affects the rate of fatigue [Fig. 2 in this study; Fig. 4 in Matar et
al. (16)] and the capacity to recover tetanic force [for 2- to 3-mo-old mice, data not shown; Fig. 6 of Matar et al.
(16)] after fatigue in EDL and soleus muscle. Second, the
resting tension increases very little during fatigue in EDL muscle of
wild-type mice, which was 1-2% of the prefatigue tetanic force
after 180 s of stimulation [Fig. 3A in this study;
Fig. 5A in Matar et al. (16)]. In the presence
of glibenclamide, resting tension increases significantly to
4.6-4.9% within 60 s [Fig. 5A in Matar et al. (16)], which is comparable to the 7.8-8.4% values
observed in Kir6.2/
EDL muscle (Fig. 3A).
Third, the difference in resting tensions between wild-type and
Kir6.2
/
soleus muscle (2- to 3-mo-old group) was not
significant throughout the fatigue stimulation (Fig. 3B),
and the same was observed between control and glibenclamide-exposed
soleus muscle [Fig. 5B of Matar et al. (16)].
Thus considering all these similarities, we suggest 1) the
lack of a glibenclamide effect on the decrease in tetanic force during
fatigue was not due to a decreased efficiency of glibenclamide to block
KATP channels; 2) the glibenclamide effect on
resting tension in EDL muscle is due to a blocking of KATP
channels and not to an increase in Ca2+ sensitivity of the
contractile apparatus; and 3) there is no evidence that the
Kir6.2/
mice compensate for the KATP
channel deficiency (at least for the fatigue kinetics).
Role of the KATP Channel in Skeletal Muscle During Fatigue
As described in the introduction, the postulated mechanism of action of the KATP channel is to reduce force development to protect against irreversible function impairment. Our results do not support this mechanism, at least during muscle fatigue, because a lack of KATP channel in the cell membrane had no effect on the rate of fatigue in EDL muscle from mice of all ages and in soleus muscle from 1-yr-old mice. Although an effect was observed in soleus muscle of 2- to 3-mo-old Kir6.2One consistent effect of the lack of KATP channel activity in the cell membrane is greater increases in resting tension during fatigue compared with control. This effect was observed in EDL muscle of both 2- to 3-mo-old and 1-yr-old mice and in soleus muscle of 1-yr-old mice (Fig. 3). Greater increases in resting tension were also observed when the channel was blocked with glibenclamide (16). The activity of KATP channels was not measured in this study because it is not possible to measure membrane potential with microelectrodes while muscles are contracting and because glibenclamide had very little effect on membrane potential and K+ efflux (16). However, considering the similarities in the effects of glibenclamide and KATP channel deficiency, we now suggest that the major function of the KATP channel during fatigue is to reduce the development of resting tension. The capacity of the KATP channel to modulate the resting tension during fatigue is further supported by the fact that an activation of the channel with pinacidil completely abolishes the development of resting tension in both EDL and soleus muscle (16).
There is evidence that the KATP channels in human suffering of hypokalemic periodic paralysis (HOPP) have abnormal characteristics (25), even though the mutation has been identified on the L-type calcium channel (13). Associated with the KATP channel abnormality is a tendency to have a depolarized cell membrane (20). Also, the cell membrane of frog sartorius muscle fibers does not depolarize during metabolic inhibition unless the KATP channels are blocked with glibenclamide. The depolarizations in the presence of glibenclamide exceeded 30 mV (9), which is large enough to activate L-type Ca2+ channels and to allow for an increase in Ca2+ influx and eventually the development of resting tension. It can then be suggested from these studies that KATP channels are important in maintaining resting potential by providing a hyperpolarizing current and that this effect is important to prevent a large development of resting tension.
Although such a mechanism may be important during metabolic inhibition, it remains to be determined whether it is also important during fatigue. Matar et al. (16) showed that blocking KATP channels only causes a 3-mV depolarization, which is too small to consider an activation of L-type Ca2+ channels unless the depolarization measured at the surface membrane with microelectrodes does not reflect the extent of the depolarization in T tubules. Thus further studies will be necessary to determine whether an effect of KATP channels on resting potential between contractions is the mechanism by which these channels affect resting tension.
A deficiency in KATP channels had no significant effect on
the twitch and tetanic force (Tables 2 and 3), as well as on the
recovery of force, after fatigue in 2- to 3-mo-old mice (data not
shown). However, the situation was different for the muscles of
1-yr-old mice. First, the tetanic forces were significantly less in EDL
and soleus muscles of 1-yr-old mice than in 2- to 3-mo-old
Kir6.2/
mice, whereas the differences in tetanic force
were not significant in muscles of wild-type mice (Table 3). Second,
the capacity to recover tetanic force after fatigue was greater in
muscles from 1-yr-old wild-type than Kir6.2
/
mice (Fig.
4). These results suggest that a KATP deficiency causes some loss of muscle function with age. It is interesting to note that
the effects of a KATP channel deficiency on muscle function was observed in mice that were mostly sedentary. In consideration of
the effect of this deficiency on the resting tension during fatigue, it
will therefore be interesting to determine in future studies whether
the deterioration of muscle function is accentuated when
Kir6.2
/
mice are subjected to chronic exercise.
As discussed above, HOPP patients have abnormal KATP
channel characteristics (25). HOPP symptoms also include
periodic paralyses and the apparition of central nuclei and vacuoles in
affected muscle (21). So far, Kir6.2/
mice
have not shown any sign of periodic paralyses, and our histological studies on muscle from 1-yr-old mice did not reveal any vacuoles or
centrally located nuclei (data not shown). Thus the HOPP symptoms do
not appear to be solely due to the abnormality observed for the
KATP channels.
In summary, this study provides evidence that the major function of the KATP channel is to reduce the increase in resting tension during fatigue and not to contribute to a decrease in force, as originally postulated. The study also shows that the capacity of skeletal muscle to generate force and to recover force after fatigue decreases with aging to a greater extent in KATP channel-deficient mice than in wild-type mice, which suggests that the KATP channel is important in protecting muscle function.
![]() |
ACKNOWLEDGEMENTS |
---|
This study was supported by a grant from the National Science and Engineering Research Council of Canada (to J. M. Renaud) and by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture, Japan (to S. Seino).
![]() |
FOOTNOTES |
---|
Address for reprint requests and other correspondence: J. M. Renaud, Dept. of Cellular and Molecular Medicine, Univ. of Ottawa, 451 Smyth Rd., Ottawa, Ontario, Canada K1H 8M5 (E-mail: jmrenaud{at}uottawa.ca).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 12 March 2000; accepted in final form 24 May 2000.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Adrian, RH,
Chandler WK,
and
Hodgkin AL.
Voltage clamp experiments in striated muscle fibres.
J Physiol (Lond)
208:
607-644,
1970[ISI][Medline].
2.
Babenko, AP,
Aguilar-Bryan L,
and
Bryan J.
A view of SUR/Kir6. X. KATP channels.
Annu Rev Physiol
60:
667-687,
1998[ISI][Medline].
3.
Burton, FL,
and
Smith GL.
The effect of cromakalim on intracellular [Ca2+] in isolated rat skeletal muscle during fatigue and metabolic blockade.
Exp Physiol
82:
469-483,
1997[Abstract].
4.
Comtois, A,
Sinderby C,
Comtois N,
Grassino A,
and
Renaud JM.
An ATP-sensitive potassium channel blocker decreases diaphragmatic circulation in anesthetized dogs.
J Appl Physiol
77:
127-134,
1994
5.
Comtois, AS,
Light PE,
and
Renaud JM.
Effect of tolbutamide on the rate of fatigue and recovery in frog sartorius muscle.
J Pharmacol Exp Ther
274:
1061-1066,
1995[Abstract].
6.
Deutsch, N,
Klitzner TS,
Lamp ST,
and
Weiss JN.
Activation of cardiac ATP-sensitive K+ current during hypoxia: correlation with tissue ATP levels.
Am J Physiol Heart Circ Physiol
261:
H671-H676,
1991
7.
Duty, S,
and
Allen DG.
The effects of glibenclamide on tetanic force and intracellular calcium in normal and fatigued mouse skeletal muscle.
Exp Physiol
80:
520-541,
1995.
8.
Gasser, RNA,
and
Vaughan-Jones RD.
Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.
J Physiol (Lond)
431:
713-741,
1990[Abstract].
9.
Gramolini, A,
and
Renaud JM.
Blocking ATP-sensitive K+ channel during metabolic inhibition impairs muscle contractility.
Am J Physiol Cell Physiol
272:
C1936-C1946,
1997
10.
Hodgkin, AL,
and
Horowicz P.
The influence of potassium and chloride ions on the membrane potential of single muscle fibres.
J Physiol (Lond)
148:
127-160,
1959[ISI][Medline].
11.
Inagaki, N,
Gonoi T,
Clement JP,
Wang CZ,
Aguilar-Bryan L,
Bryan J,
and
Seino S.
A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.
Neuron
16:
1011-1017,
1996[ISI][Medline].
12.
Inagaki, N,
Gonoi T,
Clement JP, IV,
Namba N,
Inazawa J,
Gonzalez G,
Aguilar-Bryan L,
Seino S,
and
Bryan J.
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
Science
270:
1166-1170,
1995[Abstract].
13.
Jurkat-Rott, K,
Uetz U,
Pika-Hartlaub U,
Powell J,
Fontaine B,
Melzer W,
and
Lehmann-Horn F.
Calcium currents and transients of native and heterologously expressed mutant skeletal muscle DHP receptor 1 subunits (R528H).
FEBS Lett
423:
198-204,
1998[ISI][Medline].
14.
Keung, EC,
and
Li Q.
Lactate activates ATP-sensitive potassium channels in guinea pig ventricular myocytes.
J Clin Invest
88:
1772-1777,
1991[ISI][Medline].
15.
Light, PE,
Comtois AS,
and
Renaud JM.
The effect of glibenclamide on frog skeletal muscle: evidence for K+ATP channel activation during fatigue.
J Physiol (Lond)
475:
495-507,
1994[Abstract].
16.
Matar, W,
Nosek TM,
Wong D,
and
Renaud JM.
Pinacidil suppresses contractility and preserves energy but glibenclamide has no effect during fatigue in skeletal muscle.
Am J Physiol Cell Physiol
278:
C404-C416,
2000
17.
Miki, T,
Nagashima H,
Tashiro F,
Kotake K,
Yoshitomi H,
Tamamoto A,
Gonoi T,
Iwanaga T,
Miyazaki JI,
and
Seino S.
Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice.
Proc Natl Acad Sci USA
95:
10402-10406,
1998
18.
Noma, A.
ATP-regulated K+ channels in cardiac muscle.
Nature
305:
147-148,
1983[ISI][Medline].
19.
Renaud, JM.
The effect of lactate on intracellular pH and force recovery of fatigued sartorius muscle of the frog, Rana pipiens.
J Physiol (Lond)
416:
31-47,
1989[Abstract].
20.
Ruff, RL.
Insulin acts in hypokalemic periodic paralysis by reducing inward rectifier K+ current.
Neurology
53:
1556-1563,
1999
21.
Sarnat, HB.
Muscle Pathology and Histochemistry. Chicago, IL: American Society of Clinical Pathologists Press, 1983, p. 82-83.
22.
Seino, S.
ATP-sensitive potassium channels: a model of heteromultimeric potassium channel/receptor assemblies.
Annu Rev Physiol
61:
637-662,
1999.
23.
Standen, NB,
Pettit AI,
Davies NW,
and
Stanfield PR.
Activation of ATP-dependent K+ currents in intact skeletal muscle fibres by reduced intracellular pH.
Proc R Soc Lond B Biol Sci
247:
195-198,
1992[ISI][Medline].
24.
Steel, RGD,
and
Torrie JH.
Principles and Procedures of Statistics. A Biometrical Approach. New York: McGraw-Hill, 1980, p. 173-175.
25.
Tricarico, D,
Servidei S,
Tonali P,
Jurkat-Rott K,
and
Camerino DC.
Impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in patients with hypokalemic periodic paralysis.
J Clin Invest
103:
675-682,
1999
26.
Van Lunteren, E,
Moyer M,
and
Torres A.
ATP-sensitive K+ channel blocker glibenclamide and diaphragm fatigue during normoxia and hypoxia.
J Appl Physiol
85:
601-608,
1998
27.
Venkatesh, N,
Lamp ST,
and
Weiss JN.
Sulfonylureas, ATP-sensitive K+ channels, and cellular K+ loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle.
Circ Res
69:
623-637,
1991[Abstract].
28.
Vivaudou, MB,
Arnoult C,
and
Villaz M.
Skeletal muscle ATP-sensitive K+ channels recorded from sarcolemmal blebs of split fibers: ATP inhibition is reduced by magnesium and ADP.
J Membr Biol
122:
165-175,
1991[ISI][Medline].
29.
Weselcouch, EO,
Sargent C,
Wilde MW,
and
Smith MA.
ATP-sensitive potassium channels and skeletal muscle function in vitro.
J Pharmacol Exp Ther
267:
410-416,
1993[Abstract].
30.
Westerblad, H,
Lee JA,
Lännergren J,
and
Allen DG.
Cellular mechanisms of fatigue in skeletal muscle.
Am J Physiol Cell Physiol
261:
C195-C209,
1991