Departments of 1 Veterinary PathoBiology and 2 Physiology, University of Minnesota, St. Paul, Minnesota 55108
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Modulation of the L-type current by sarcoplasmic
reticulum (SR) Ca2+ release has
been examined in patch-clamped mouse myotubes. Inhibition of SR
Ca2+ release by inclusion of
ryanodine in the internal solution shifted the half-activating voltage
(V0.5) of the
L-type current from 1.1 ± 2.1 to 7.7 ± 1.7 mV. Ruthenium
red in the internal solution shifted
V0.5 from 5.4 ± 1.9 to
3.2 ± 4.1 mV. Chelation of myoplasmic Ca2+ with
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic
acid perfusion shifted
V0.5 from 4.4 ± 1.7 to
3.5 ± 3.3 mV and increased the peak current.
Extracellular caffeine (1 mM), which should enhance SR
Ca2+ release, significantly
decreased the peak Ca2+ current.
In low (0.1 mM) internal EGTA, myotube contraction was abolished by
internal perfusion with ryanodine or ruthenium red, whereas addition of
caffeine to the extracellular solution lowered the contractile
threshold, indicating that these modulators of SR
Ca2+ release had the expected
effects on contraction. Therefore, SR Ca2+ release appears to modulate
the sarcolemmal L-type current, suggesting a retrograde communication
from the SR to the sarcolemmal L-type channels in
excitation-contraction coupling.
excitation-contraction coupling; ryanodine receptor; dihydropyridine receptor
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
OPENING OF THE SARCOPLASMIC RETICULUM (SR) Ca2+ release channels/ryanodine receptors in skeletal muscle is thought to be initiated by a voltage-driven conformational change in the dihydropyridine receptor (DHPR) of the transverse tubules (t-tubules) (20, 23). The movement of charged residues of the DHPR across the electric field of the sarcolemma can be measured as an electric signal and is referred to as the t-tubular charge movement. The conformational change of the DHPRs is thought to be transmitted to and to trigger the opening of the SR Ca2+ release channels via direct physical coupling (24, 27). Although not all the Ca2+ release channels appear to be physically linked to DHPRs (2), Ca2+ flowing out of coupled Ca2+ release channels is thought to activate neighboring uncoupled Ca2+ release channels by Ca2+-induced Ca2+ release. A rise in the Ca2+ concentration in the triadic junction is followed by an elevation of myoplasmic Ca2+ and muscle contraction.
Signaling from the t-tubule to the SR has been well studied (15, 25). More recently, retrograde SR-to-t-tubule communication has been suggested (25). A component of the t-tubular charge movement is hypothesized to be the result of Ca2+ released from the SR binding to the DHPRs and initiating additional charge movement (25). In addition to functioning as the voltage sensor for gating of Ca2+ release channels, the DHPR is also an L-type Ca2+ channel. In frog skeletal muscle fibers, drugs that potentiate SR Ca2+ release enhance the L-type current, whereas agents that diminish SR Ca2+ release reduce the L-type current (11). This suggests that the L-type current may be regulated by the Ca2+ concentration in the triadic junction. In myotubes from transgenic mice lacking the skeletal muscle isoform of the SR Ca2+ release channel, the L-type current was greatly reduced, with no change in quantity of charge movement (22), an indicator of the number of functional DHPRs. However, in myotubes lacking the SR Ca2+ release channels, the architecture of the triads may have been disrupted to such an extent as to render the DHPRs nonfunctional as ion channels. The results obtained with transgenic mouse myotubes and adult frog muscle fibers agree with respect to the effect of disruption of SR Ca2+ release on the L-type current. Nevertheless, care must be taken when the two preparations are compared, since the mechanisms of excitation-contraction coupling in mammalian myotubes and mature amphibian muscle fibers may not be identical (8, 33).
To investigate a possible relationship between SR Ca2+ release and DHPR function in mammalian cells with the normal excitation-contraction coupling architecture, we examined the effects of altered SR Ca2+ release on the L-type current in cultured mouse myotubes. We found that agents known to decrease SR Ca2+ release shifted the voltage dependence of activation of the L-type current to more negative potentials, whereas enhancing SR Ca2+ release decreased the peak L-type current. These results suggest retrograde communication between the SR and the t-tubular L-type channel.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Culture of mouse myotubes. Limb muscles from 1- to 3-day-old mice were enzymatically and mechanically dissociated, then subjected to differential centrifugation and resuspension. Cells were plated at 1-3 × 105 cells/35-mm culture plate in mouse plating medium [83% Dulbecco's modified Eagle's medium with 4.5 g/l glucose (DMEM), 15% FCS, 100 U/ml penicillin, 10 µg/ml streptomycin]. After 24 h in culture, plates were rinsed with Ca2+- and Mg2+-free rodent Ringer solution (in mM: 155 NaCl, 5 KCl, 10 HEPES, pH 7.4) and the medium was changed to DMEM with 10% FCS. When cultures were near confluence, fusion was induced by changing the medium to mouse maintenance medium (88% DMEM, 10% horse serum, 100 U/ml penicillin, 10 µg/ml streptomycin). In some cases, cells were frozen in liquid nitrogen and cultured at a later date. Myotubes were studied 4-9 days after the initiation of fusion.
Patch-clamp methods.
Currents were recorded by the whole cell variant of the patch-clamp
technique using an Axopatch 1-C patch-clamp amplifier and TL-1
interface or an Axopatch 200A patch-clamp amplifier and Digidata 1200 interface and pClamp 5.5 acquisition and analysis software (Axon
Instruments). Linear capacitive and leakage currents were obtained from
a series of control pulses and subtracted from the currents produced by
incremental depolarizing test pulses from the holding potential
(80 mV). Effective series resistance was reduced by electronic
compensation. Linear capacity of each cell was determined via a 20-mV
hyperpolarizing pulse from the holding potential. The area under the
resulting current transient yielded the total linear capacitance of the
cell and provided an estimate of the cell's membrane area. Compact
cells with a capacitance of 200-700 pF were studied, and currents
were normalized by expression in capacitance-specific units (pA/pF) to
correct for differences in cell size. A pipette puller (model P-97,
Sutter Instruments) was used to pull pipettes from borosilicate glass; the pipettes had a resistance of 1.6-2.6 M
when filled with the experimental solution. Agar-bridge electrodes were used for a ground.
Analysis. The I-V relationships were fitted with the equation
![]() |
(1) |
|
|
|
|
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Effects of SR
Ca2+ release
inhibitors on the L-type current.
The inclusion of 1 mM ryanodine in the internal solution shifted
V0.5
to more negative potentials (Table 1)
without altering the peak current. Figure
1A shows current responses to a
voltage step from 80 to 0 mV with an internal solution
containing 1 mM ryanodine. Current was ~80% larger at 5 min
(bottom trace) than at 2 min
(top trace) after perfusion with
ryanodine. In the absence of ryanodine, current responses to the same
voltage step did not change significantly over the same time period
(Fig. 1A, inset). In the presence
of ryanodine,
V0.5
of the Ca2+ current was
significantly shifted to more negative potentials (Fig.
1B, Table 1) with no change in the
peak current (
10.9 ± 1.1 and
11.8 ± 1.2 pA/pF initial and final peak currents, respectively). In the absence of
ryanodine, over the same time period, there was a small but
statistically significant shift in
V0.5
in the same direction, also with no change in the peak
Ca2+ current (
8.5 ± 1.0 and
8.8 ± 1.1 pA/pF initial and final peak currents,
respectively). However, the magnitude of the shift in the presence of
ryanodine (8.7 ± 1.9 mV) was significantly greater (P = 0.006) than in the absence of
ryanodine (4.2 ± 1.3 mV). None of the other parameters of
Eq. 1 was significantly altered in the
presence or absence of ryanodine. The effects of ryanodine on the
I-V relationship could not be
attributed to cell damage, since neither the cell capacitance
(Cm)
nor the holding current (Ih)
was significantly altered over the course of the experiment. The
initial
Cm
and Ih were 493 ± 51 pF and
1.47 ± 0.42 pA/pF, respectively. The final
Cm
and Ih were 611 ± 85 pF and -1.14 ± 0.33 pA/pF, respectively. Similarly,
neither measure was altered over the course of the experiment in the
absence of ryanodine. Initial and final
Cm
values were 472 ± 51 and 465 ± 39 pF, respectively. Initial and
final Ih values were
1.60 ± 0.36 and
1.37 ± 0.37 pA/pF, respectively. Similar results
were obtained in 10 experiments in which
Ba2+ was used as the current
carrier (data not shown), indicating that the ryanodine-induced shift
in the voltage dependence of the L-type current did not depend on the
species of ion carrying the current.
|
Effects of the fast
Ca2+ chelator
BAPTA.
Ryanodine and ruthenium red inhibit
Ca2+ release by directly
interacting with the Ca2+ release
channel (17, 28). This could result in an altered conformation of the
Ca2+ release channel and,
therefore, affect the L-type current by modifying the interaction
between the Ca2+ release channel
and the L-type channel. Alternatively, ryanodine and ruthenium red
block SR Ca2+ release and decrease
triadic Ca2+, which in turn might
be responsible for the shift in the L-type current
V0.5
to more negative potentials. To discriminate between these two
possibilities, we sought to buffer the SR
Ca2+ release-induced rise in the
triadic Ca2+ concentration without
direct drug interaction with the
Ca2+ release channel. To do this,
we included 20 mM BAPTA in the internal solution while maintaining the
free Ca2+ concentration. This
maneuver shifted
V0.5
to a more negative voltage in a manner similar to blocking the
Ca2+ release channel with
ryanodine or ruthenium red (Fig. 3, Table 1). In addition, in the
presence of BAPTA, over time the maximal current was significantly
increased (10.7 ± 1.0 and
13.0 ± 1.39 pA/pF
initial and final maximal currents, respectively,
P = 0.01). Because none of the other
parameters of Eq. 1 was altered by
BAPTA, this increase can be attributed to the leftward shift in
V0.5. In experiments with 8 mM EGTA in the internal solution, there were no
significant changes in the peak
Ca2+ current (
9.1 ± 0.8 and
8.7 ± 1.1 pA/pF initial and final currents, respectively) or the I-V relationship
over the same time period. In experiments in which BAPTA was included
in the internal solution, there was no significant change in
Cm
(434 ± 33 and 391 ± 31 pF initial and final
Cm,
respectively). However, there was a significant decrease in
Ih (
3.10 ± 0.66 and
1.97 ± 0.42 pA/pF initial and final
Ih,
respectively). When the internal solution contained EGTA, there was no
significant change in
Cm
(319 ± 40 and 329 ± 48 pF initial and final
Cm,
respectively) or
Ih (
5.00 ± 0.64 and
4.59 ± 0.55 pA/pF initial and final
Ih, respectively).
Effects of stimulation of SR
Ca2+ release.
To enhance SR Ca2+ release, after
the L-type current was recorded in the control external solution, the
experimental chamber was perfused with 10 vol of external solution
containing 1 mM caffeine. Caffeine did not alter
V0.5
but, rather, decreased the peak current (Fig. 4). In the experiment
shown in Fig. 4A, caffeine decreased
the current in response to a voltage step to +20 mV by ~40%.
Perfusing the chamber without including caffeine slightly increased the
current in the experiment illustrated in Fig. 4A, inset. Several attempts were made to reverse the
caffeine-induced reduction in peak
Ca2+ current; although we were
generally unsuccessful, the caffeine effect was partially reversed on
two occasions (data not shown). Addition of caffeine decreased the peak
current ~25% (11.6 ± 1.3 and
8.4 ± 0.8 pA/pF
initial and final peak currents, respectively), and
gmax
decreased significantly (~30%) compared with controls (Fig.
4B, Table 1). Changing solutions
without including caffeine did not significantly alter the peak
Ca2+ current (
10.6 ± 0.9 and
10.5 ± 0.8 pA/pF initial and final peak currents,
respectively) or the I-V relationship
(Table 1, Fig. 4B, inset).
Importantly, neither
Cm
nor
Ih
was significantly altered by changing the external solution with
caffeine (initial Cm = 338 ± 42 pF and
Ih =
0.94 ± 0.38 pA/pF; final
Cm = 329 ± 42 pF and
Ih =
0.81 ± 0.51 pA/pF) or without caffeine (initial Cm = 411 ± 74 pF and
Ih =
1.00 ± 0.52 pA/pF; final
Cm = 424 ± 69 pF and
Ih =
0.67 ± 0.49 pA/pF).
Effects of the drugs on contraction.
To establish that the modulators of SR
Ca2+ release had the expected
effect on SR Ca2+ release
(decreased release in the presence of ryanodine and ruthenium red and
increased release in the presence of caffeine), the concentration of
EGTA in the internal solution was reduced to 0.1 mM to allow contraction. Cells contracted in response to periodic stimulation (50-ms pulse from 80 to 0 mV) for up to 20 min. However, when ryanodine (1 mM) was included in the pipette, contraction was visibly
reduced after a few minutes and completely abolished by ~10
min. Ruthenium red (200 µM) required ~20 min to inhibit
contraction. These results strongly suggest that ryanodine and
ruthenium red significantly reduced SR
Ca2+ release in these myotubes.
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
We have examined the effects of SR Ca2+ release on the L-type current. Agents that reduced SR Ca2+ release, i.e., ruthenium red or high concentrations of ryanodine, were included in the pipette. The "fast" Ca2+ chelator BAPTA was used to buffer Ca2+ as it was released from the SR and presumably to reduce triadic Ca2+ concentration. SR Ca2+ release was enhanced by the addition of caffeine to the external solution at a concentration that did not directly trigger SR Ca2+ release. Decreased Ca2+ release or highly buffered triadic Ca2+ resulted in a negative shift in V0.5, whereas enhanced SR Ca2+ release resulted in a reduced magnitude of the L-type current. Our results indicate that interventions that presumably alter triadic Ca2+ concentrations modulate the L-type current in mouse myotubes. Thus there appears to be communication not only from the sarcolemmal L-type channel to the SR Ca2+ release channel but also from the SR Ca2+ release channel back to the sarcolemmal L-type channel.
The observed shifts in the L-type I-V relationship could be explained by 1) drug-induced changes in Ca2+ release channel structure being transmitted back to the DHPR, via a mechanical coupling, to alter L-type channel function, 2) changes in the triadic Ca2+ concentration, or 3) effects of these agents unrelated to Ca2+ release channel function. Ryanodine, ruthenium red, and caffeine bind to specific sites on the Ca2+ release channel and could modify the L-type current by altering the physical interaction between the Ca2+ release channel and the L-type channel (24). Ryanodine and ruthenium red block the Ca2+ release channel, decrease Ca2+ release, and shift the L-type current activation to more negative potentials. BAPTA, however, does not interact with the Ca2+ release channel but chelates Ca2+ as it is released from the SR [although not 100% effective at the concentration used in this study (30)] and has an effect on the L-type current similar to that of ryanodine and ruthenium red. Thus the observations with BAPTA demonstrate that direct interaction with the SR Ca2+ release channel is not a requirement for the observed alterations in the sarcolemmal L-type current.
Ryanodine and ruthenium red bind to specific sites on the Ca2+ release channel (18, 19). Ryanodine at low concentrations can lock the Ca2+ release channel in a low-conductance substate, whereas high concentrations can block the channel. Ruthenium red's sole effect on the Ca2+ release channel is blocking the conductance. Although the concentration of ryanodine at the Ca2+ release channel in these experiments is unknown, the use of millimolar ryanodine concentration in the internal solution, the observed block of contraction, and the similar effect on the L-type current by ruthenium red suggest that SR Ca2+ release was blocked by ryanodine. It is unlikely that the observed effects of ryanodine on the L-type current can be attributed to direct stimulation of the L-type channel, because ryanodine has been shown to decrease the single channel percent open time of purified DPHRs in planar lipid bilayers (34). Likewise, ruthenium red has been shown to inhibit the L-type current in bovine adrenal chromaffin cells with no shift in the I-V relationship (14). Therefore, if in the present experiments ryanodine and/or ruthenium red was interacting with the DHPR, gmax should have been reduced. In contrast, a shift in V0.5 with no significant change in gmax was observed. In addition, BAPTA also caused a negative shift in V0.5 in a manner similar to ryanodine and ruthenium red. Because BAPTA does not bind the DHPR or SR Ca2+ release channel, the effects of BAPTA must be due to its ability to blunt the rise in triadic Ca2+. The simplest way to explain the similar effects of ryanodine, ruthenium red, and BAPTA on the L-type current is to suggest a common mechanism, i.e., a smaller rise in triadic Ca2+.
The mechanism by which a decrease in triadic Ca2+ modulates the L-type current is unclear. It may involve a direct interaction of Ca2+ with the L-type channel or modulation of the activity of a Ca2+-dependent kinase or phosphatase, which could alter the phosphorylation status of the channel. In this regard, it is interesting to note that high concentrations of BAPTA had complex effects on the intramembranous charge movement of skeletal muscle; among these was a negative shift in V0.5 (31, 32). These effects were attributed to the ability of BAPTA to buffer the rise in triadic Ca2+ and prevent Ca2+ binding to a specific site on the DHPR. Although the relationship between the charge movement and L-type current is not well understood and the exact mechanism by which triadic Ca2+ may modulate the L-type current is not clear, these findings support the conclusion that triadic Ca2+ can modulate the function of the DHPR.
Caffeine also binds to the Ca2+ release channel but, in contrast to ryanodine and ruthenium red, stimulates SR Ca2+ release (26). However, methylxanthines also inhibit phosphodiesterase and can lead to an elevation of cAMP (4). Because the skeletal muscle L-type channel can be phosphorylated by cAMP-dependent protein kinase A (PKA) (7), an increase in intracellular cAMP could possibly modulate the L-type current. The caffeine concentration used here (1 mM) inhibits purified phosphodiesterase by ~20% (4). However, it is unlikely that the decreased L-type current observed here in the presence of caffeine was due to PKA-catalyzed phosphorylation. Previous studies have shown that cAMP stimulates the L-type current in adult frog skeletal muscle fibers (16) and has no effect on the L-type current in rat myoballs (29), whereas PKA phosphorylation of purified DHPRs increases the percent open time and shifts the voltage dependence to more negative potentials (21). Thus, if the effects of caffeine were mediated by PKA, the L-type current would have been increased rather than decreased.
The poor reversibility of the caffeine-induced reduction in peak current may be due in part to the activation of Ca2+-sensitive phosphatases and/or proteases. High intracellular Ca2+ concentrations are associated with a rapid decline in the whole cell Ca2+ current, with no change in the amplitude of the single-channel current, suggesting a decrease in the number of L-type channels available for activation (12). Furthermore, conditions favorable for channel phosphorylation or the addition of protease inhibitors slowed the decline in current amplitude (5, 6), thereby implicating Ca2+-activated phosphatases and proteases in the current decline. These observations suggest a mechanism by which caffeine may have led to the decrease in gmax. Caffeine enhances SR Ca2+ release and should cause a rise in triadic Ca2+. Such an increase could activate Ca2+-sensitive phosphatases and/or proteases, although the rate at which caffeine induced the decline in Ca2+ current is more comparable to the time course of the Ca2+-dependent dephosphorylation. Dephosphorylation of the L-type channels would then decrease the number of channels available for activation and thereby reduce gmax. Such a mechanism may be physiologically relevant in muscle disorders such as malignant hyperthermia, where the rate of SR Ca2+ release is enhanced compared with normal muscle (10), or in severe muscle fatigue, when resting Ca2+ is elevated (35). In both cases, it would be advantageous to reduce the amount of Ca2+ entering the cell and prevent further elevations in triadic Ca2+.
In contrast to our observation that increased SR Ca2+ release is associated with a decrease in the sarcolemmal L-type current, Feldmeyer et al. (11) reported that increased SR Ca2+ release enhanced the L-type current in adult frog skeletal muscle fibers. The discrepancy may be due to a species or developmental difference. Amphibian skeletal muscle fibers contain roughly equal amounts of two SR Ca2+ release channel isoforms, whereas mammalian skeletal muscle fibers contain almost exclusively one isoform (33). In contrast to adult muscle fibers, excitation-contraction coupling in myotubes appears to have a significant cardiac-like component. In skeletal muscle myotubes, 9 days after the initiation of fusion, ~40-45% of contraction could be abolished by blocking the L-type current (8). This component of contraction was dramatically diminished as the myotubes matured. The presence of the cardiac-like component of excitation-contraction coupling may necessitate an interaction between the Ca2+ release channel and DHPR in the developing myotube different from that in the adult skeletal muscle fiber and may account for the differences between the present study and that of Feldmeyer et al.
Although the physiological function of the L-type current in mature skeletal muscle fibers is unclear, Constantin et al. (9) proposed that the L-type current serves to fill the intracellular Ca2+ stores in developing muscle cells. Our results are consistent with that proposal. A depletion of SR Ca2+ would result in decreased SR Ca2+ release on plasma membrane depolarization, resulting in a smaller rise in triadic Ca2+, which in turn would stimulate Ca2+ influx via the L-type channel. Such an effect on triadic Ca2+ was mimicked in experiments where SR Ca2+ release was blocked by ryanodine or ruthenium red or when triadic Ca2+ was buffered by BAPTA. Conversely, if excess SR Ca2+ release occurs, the L-type current might be depressed, as in the experiments in the presence of caffeine.
In conclusion, our results support the hypothesis of a retrograde communication between the SR Ca2+ release channel and the DHPR. This communication may be mediated in some cases by a direct interaction between the two channel proteins (22), but it may also be communicated by the Ca2+ concentration in the triadic junction.
![]() |
ACKNOWLEDGEMENTS |
---|
We thank Jon Snover and Grace Wu for providing technical support and cultured myotubes and Drs. Charles Louis, James Mickelson, and Bradley Fruen for critical reading of the manuscript and helpful comments.
![]() |
FOOTNOTES |
---|
This work was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant RO1 AR-41270 (E. M. Gallant).
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. §1734 solely to indicate this fact.
Address for reprint requests: E. M. Balog, Dept. of Veterinary PathoBiology, 1988 Fitch Ave., ASVM Bldg., Rm. 295, St. Paul, MN 55108.
Received 20 March 1998; accepted in final form 9 October 1998.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Baylor, S. M.,
S. Hollingworth,
and
M. W. Marshall.
Effects of intracellular ruthenium red on excitation-contraction coupling in intact frog skeletal muscle fibers.
J. Physiol. (Lond.)
344:
625-666,
1983[Abstract].
2.
Block, B. A.,
T. Imagawa,
K. P. Campbell,
and
C. Franzini-Armstrong.
Structural evidence for direct interaction between the molecular components of the transverse tubular/sarcoplasmic reticulum junction in skeletal muscle.
J. Cell Biol.
107:
2587-2600,
1988[Abstract].
3.
Brooks, S. P. J.,
and
K. B. Storey.
Bound and determined: a computer program for making buffers of defined ion concentrations.
Anal. Biochem.
201:
119-126,
1992[Medline].
4.
Butcher, R. W.,
and
E. W. Sutherland.
Adenosine 3',5'-phosphate in biological materials.
J. Biol. Chem.
237:
1244-1250,
1962
5.
Byerly, L.,
and
B. Yazejian.
Intracellular factors for the maintenance of calcium currents in perfused neurons from the snail, Lymnae stagnalis.
J. Physiol. (Lond.)
370:
631-650,
1986[Abstract].
6.
Chad, J. E.,
and
R. Eckert.
An enzymatic mechanism for calcium current inactivation in dialysed Helix neurons.
J. Physiol. (Lond.)
378:
31-51,
1986[Abstract].
7.
Chang, C. F.,
L. M. Gutierrez,
C. Mundina-Weilenmann,
and
M. M. Hosey.
Dihydropyridine-sensitive calcium channels from skeletal muscle. II. Functional effects of differential phosphorylation of channel subunits.
J. Biol. Chem.
266:
16395-16400,
1991
8.
Cognard, C.,
M. Rivet-Bastide,
B. Constantin,
and
G. Raymond.
Progressive predominance of "skeletal" versus "cardiac" types of excitation-contraction coupling during in vitro skeletal myogenesis.
Pflügers Arch.
422:
207-209,
1992[Medline].
9.
Constantin, B.,
C. Cognard,
M. Rivet-Bastide,
and
G. Raymond.
Calcium current-dependent staircase in rat myotubes and myoballs developing in culture.
Cell Calcium
14:
135-144,
1993[Medline].
10.
Endo, M.,
S. Yagi,
T. Ishizuka,
K. Horiuti,
Y. Koga,
and
K. Amaha.
Changes in the Ca-induced Ca release mechanism in the sarcoplasmic reticulum of muscle from a patient with malignant hyperthermia.
Biomed. Res.
4:
83-92,
1983.
11.
Feldmeyer, D.,
W. Melzer,
B. Pohl,
and
P. Zollner.
A possible role of sarcoplasmic Ca2+ release in modulating the slow Ca2+ current of skeletal muscle.
Pflügers Arch.
425:
54-61,
1993[Medline].
12.
Fenwick, E. M.,
A. Marty,
and
E. Neher.
Sodium and calcium channels in bovine chromaffin cells.
J. Physiol. (Lond.)
331:
599-635,
1982[Medline].
13.
Gallant, E. M.,
N. S. Taus,
T. F. Fletcher,
L. R. Lentz,
C. F. Louis,
and
J. R. Mickelson.
Perchlorate potentiation of excitation-contraction coupling in mammalian skeletal muscles.
Am. J. Physiol.
264 (Cell Physiol. 33):
C559-C567,
1993
14.
Gomis, A.,
L. Gutierrez,
F. Sala,
S. Viniegra,
and
J. A. Reig.
Ruthenium red inhibits selectively chromaffin cell calcium channels.
Biochem. Pharmacol.
47:
225-231,
1994[Medline].
15.
Huang, C. L.-H.
Intramembrane Charge Movements in Striated Muscle. Oxford, UK: Clarendon, 1993.
16.
Kokate, T. G.,
J. A. Heiny,
and
N. Sperelakis.
Stimulation of the slow calcium current in bullfrog skeletal muscle fibers by cAMP and cGMP.
Am. J. Physiol.
265 (Cell Physiol. 34):
C47-C53,
1993
17.
Ma, J.
Block by ruthenium red of the ryanodine-activated calcium release channel of skeletal muscle.
J. Gen. Physiol.
102:
1031-1056,
1993[Abstract].
18.
Mack, M.,
I. Zimanyi,
and
I. Pessah.
Discrimination of multiple binding sites of antagonists of the calcium release channel complex of skeletal and cardiac sarcoplasmic reticulum.
J. Pharmacol. Exp. Ther.
262:
1028-1037,
1992[Abstract].
19.
Meissner, G.,
and
A. El-Hashem.
Ryanodine as a functional probe of the skeletal muscle sarcoplasmic reticulum Ca2+ release channel.
Mol. Cell. Pharmacol.
114:
119-123,
1992.
20.
Melzer, W.,
A. Herrmann-Frank,
and
H. C. Luttgau.
The role of Ca2+ ions in excitation-contraction coupling of skeletal muscle fibers.
Biochim. Biophys. Acta
1241:
59-116,
1995[Medline].
21.
Mundina-Weilenmann, C.,
J. Ma,
E. Rios,
and
M. M. Hosey.
Dihydropyridine-sensitive skeletal muscle Ca2+ channels in polarized planar bilayers. 2. Effects of phosphorylation by cAMP-dependent protein kinase.
Biophys. J.
60:
902-909,
1989[Abstract].
22.
Nakai, J.,
R. T. Dirksen,
H. T. Nguyen,
I. N. Pessah,
K. G. Beam,
and
P. D. Allen.
Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor.
Nature
380:
72-75,
1996[Medline].
23.
Rios, E.,
and
G. Brum.
Involvement of dihydropyridine receptors in excitation-contraction coupling in skeletal muscle.
Nature
325:
717-720,
1987[Medline].
24.
Rios, E.,
J. Ma,
and
A. Gonzalez.
The mechanical hypothesis of excitation-contraction coupling in skeletal muscle.
J. Muscle Res. Cell Motil.
12:
127-135,
1991[Medline].
25.
Rios, E.,
and
G. Pizarro.
Voltage sensor of excitation-contraction coupling in skeletal muscle.
Physiol. Rev.
71:
849-908,
1991
26.
Rousseau, E.,
J. Ladine,
Q. Liu,
and
G. Meissner.
Activation of the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum by caffeine and related compounds.
Arch. Biochem. Biophys.
267:
75-86,
1988[Medline].
27.
Schneider, M. F.,
and
W. K. Chandler.
Voltage dependent charge movement in skeletal muscle: a possible step in excitation-contraction coupling.
Nature
242:
244-246,
1973[Medline].
28.
Smith, J. S.,
T. Imagawa,
J. Ma,
M. Fill,
K. P. Cambell,
and
R. Coronado.
Purified ryanodine receptor from rabbit skeletal muscle is the calcium-release channel of sarcoplasmic reticulum.
J. Gen. Physiol.
92:
1-26,
1988[Abstract].
29.
Somasundaram, B.,
and
R. T. Tregear.
Isoproterenol and GTPS inhibits L-type calcium channels of differentiating rat skeletal muscle cells.
J. Muscle Res. Cell Motil.
14:
341-346,
1993[Medline].
30.
Stern, M. D.
Buffering of calcium in the vicinity of a channel pore.
Cell Calcium
13:
183-192,
1992[Medline].
31.
Stroffekova, K.,
and
J. A. Heiny.
Triadic Ca2+ modulates charge movement in skeletal muscle.
Gen. Physiol. Biophys.
16:
59-77,
1997[Medline].
32.
Stroffekova, K.,
and
J. A. Heiny.
Stimulation-dependent redistribution of charge movement between unavailable and available states.
Gen. Physiol. Biophys.
16:
79-89,
1997[Medline].
33.
Sutko, J. L.,
and
J. A. Airey.
Ryanodine receptor Ca2+ release channels: does diversity in form equal diversity in function?
Physiol. Rev.
76:
1027-1060,
1996
34.
Valdivia, H. H.,
and
R. Coronado.
Inhibition of dihydropyridine-sensitive calcium channels by the plant alkaloid ryanodine.
FEBS Lett.
244:
333-337,
1989[Medline].
35.
Westerblad, H.,
and
D. G. Allen.
Changes of myoplasmic calcium concentration during fatigue in single mouse muscle fibers.
J. Gen. Physiol.
98:
615-635,
1991[Abstract].