Appearance of the slow Ca conductance in myotubes from mutant mice with ?muscular dysgenesis?

Bournaud, Roland; Shimahara, Takeshi; Garcı́a, Luis; Rieger, François

doi:10.1007/bf00585050

Cited by 15 publications

(3 citation statements)

References 28 publications

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“…The sustained currents of the two mutant cells, here identified as I ␤null and I dys , were much smaller than the L-type current of normal cells. This result is in agreement with previous studies performed separately in dysgenic and ␤ 1 -null myotubes in culture (Bournaud et al, 1989;Beurg et al, 1997). L-type and T-type components were not always present in each cell.…”

Section: Figuresupporting

confidence: 94%

Molecular Origin of the L-Type Ca2+ Current of Skeletal Muscle Myotubes Selectively Deficient in Dihydropyridine Receptor β1a Subunit

Strube

Beurg

Sukhareva

et al. 1998

Biophysical Journal

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The origin of Ibetanull, the Ca2+ current of myotubes from mice lacking the skeletal dihydropyridine receptor (DHPR) beta1a subunit, was investigated. The density of Ibetanull was similar to that of Idys, the Ca2+ current of myotubes from dysgenic mice lacking the skeletal DHPR alpha1S subunit (-0.6 +/- 0.1 and -0.7 +/- 0.1 pA/pF, respectively). However, Ibetanull activated at significantly more positive potentials. The midpoints of the GCa-V curves were 16.3 +/- 1.1 mV and 11.7 +/- 1.0 mV for Ibetanull and Idys, respectively. Ibetanull activated significantly more slowly than Idys. At +30 mV, the activation time constant for Ibetanull was 26 +/- 3 ms, and that for Idys was 7 +/- 1 ms. The unitary current of normal L-type and beta1-null Ca2+ channels estimated from the mean variance relationship at +20 mV in 10 mM external Ca2+ was 22 +/- 4 fA and 43 +/- 7 fA, respectively. Both values were significantly smaller than the single-channel current estimated for dysgenic Ca2+ channels, which was 84 +/- 9 fA under the same conditions. Ibetanull and Idys have different gating and permeation characteristics, suggesting that the bulk of the DHPR alpha1 subunits underlying these currents are different. Ibetanull is suggested to originate primarily from Ca2+ channels with a DHPR alpha1S subunit. Dysgenic Ca2+ channels may be a minor component of this current. The expression of DHPR alpha1S in beta1-null myotubes and its absence in dysgenic myotubes was confirmed by immunofluorescence labeling of cells.

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Section: Figuresupporting

confidence: 94%

Molecular Origin of the L-Type Ca2+ Current of Skeletal Muscle Myotubes Selectively Deficient in Dihydropyridine Receptor β1a Subunit

Strube

Beurg

Sukhareva

et al. 1998

Biophysical Journal

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“…Presumably the fibroblasts provide an extracellular matrix resembling that present during muscle development in vivo because Ic~y, is frequently present in acutely dissociated dysgenic muscle fibers. A similar extracellular environment may be present to a lesser extent in conventional cultures (grown directly on plastic dishes) in which dysgenic fibroblasts have proliferated; such an occurrence may explain the report of Bournaud et al (1988) of "partial restoration of the slow calcium current" in aged cultures of dysgenic myotubes, and may also explain why we occasionally recorded Ic~.~ from dysgenic myotubes grown on untreated culture dishes. Beam et al (1986) did not describe a calcium current in dysgenic myotubes corresponding to Ic~, probably because their myotubes were grown directly on untreated culture dishes in the absence of fibroblasts.…”

Section: Comparison Of Ic~~ With Other Calcium Currentsmentioning

confidence: 81%

A novel calcium current in dysgenic skeletal muscle.

Adams

Beam

1989

The Journal of General Physiology

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The whole-cell patch-clamp technique was used to study voltagedependent calcium currents in primary cultures of myotubes and in freshly dissociated skeletal muscle from normal and dysgenic mice. In addition to the transient, dihydropyridine (DHP)-insensitive calcium current previously described, a maintained DHP-sensitive calcium current was found in dysgenic skeletal muscle. This current, here termed Ic~,t,, is largest in acutely dissociated fetal or neonatal dysgenic muscle and also in dysgenic myotubes grown on a substrate of killed fibroblasts. In dysgenic myotubes grown on untreated plastic culture dishes, Ic~ is usually so small that it cannot be detected. In addition, Ic~ay, is apparently absent from normal skeletal muscle. From a holding potential of -80 mV, Ic~.,a becomes apparent for test pulses to ~-20 mV and peaks at ~ + 20 mV. The current activates rapidly (rise time ~5 ms at 20~ and with 10 mM Ca as charge cattier inactivates little or not at all during a 200-ms test pulse. Thus, Ic~.,~ activates much faster than the slowly activating calcium current of normal skeletal muscle and does not display Ca-dependent inactivation like the cardiac L-type calcium current.

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“…Previous studies (Powell and Fambrough, 1973;Tanabe et al, 1988) have shown that dysgenic myotubes bathed in physiological saline (containing ~ 2 mM calcium) are incapable of contracting either spontaneously or in response to electrical stimulation. However, the recent discovery of a DHP-sensitive calcium current (/ca-d,) in dysgenic skeletal muscle (Adams and Beam, 1989;Bournaud et al, 1989) led us to re-examine whether dysgenic myotubes could ever display E-C coupling under less physiological conditions. Specifically, we tested whether contractions could be triggered by calcium entry through the ICa-dys channels, or through a more direct interaction of the DHP receptor underlying Ica.dys with the SR.…”

Section: Depolarization-evoked Contractions Of Dysgenic Skeletal Musclementioning

confidence: 99%

Contractions of dysgenic skeletal muscle triggered by a potentiated, endogenous calcium current.

Adams

Beam

1991

The Journal of General Physiology

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The dihydropyridine (DHP) receptor of normal skeletal muscle is hypothesized to function as the voltage sensor for excitation--contraction (E-C) coupling, and also as the calcium channel underlying a slowly activating, DHPsensitive current (termed/ca-,). Skeletal muscle from mice with muscular dysgenesis lacks both E-C coupling and/ca.,. However, dysgenic skeletal muscle does express a small DHP-sensitive calcium current (termed Ica.ays) which is kinetically and pharmacologically distinct from /Ca-," We have examined the ability of Ica.a,, or the DHP receptor underlying it, to couple depolarization and contraction. Under most conditions Ica_a, is small (~ 1 pA/pF) and dysgenic myotubes do not contract in response to sarcolemmal depolarization. However, in the combined presence of the DHP agonist Bay K 8644 (1 0.M) and elevated external calcium (10 mM), Ica~y, is strongly potentiated and some dysgenic myotubes contract in response to direct electrical stimulation. These contractions are blocked by removing external calcium, by adding 0.5 mM cadmium to the bath, or by replacing Bay K 8644 with the DHP antagonist (+)-PN 200-110. Only myotubes having a density of Ica-dys greater than ~4 pA/pF produce detectible contractions, and the strength of contraction is positively correlated with the density of Ic~-dy~, Thus, unlike the contractions of normal myotubes, the contractions of dysgenic myotubes require calcium entry. These results demonstrate that the DHP receptor underlying Ica.d, is unable to function as a "voltage sensor" that directly couples membrane depolarization to calcium release from the sarcoplasmic reticulum.

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Appearance of the slow Ca conductance in myotubes from mutant mice with ?muscular dysgenesis?

Cited by 15 publications

References 28 publications

Molecular Origin of the L-Type Ca2+ Current of Skeletal Muscle Myotubes Selectively Deficient in Dihydropyridine Receptor β1a Subunit

Molecular Origin of the L-Type Ca2+ Current of Skeletal Muscle Myotubes Selectively Deficient in Dihydropyridine Receptor β1a Subunit

A novel calcium current in dysgenic skeletal muscle.

Contractions of dysgenic skeletal muscle triggered by a potentiated, endogenous calcium current.

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