Differential modulation of a sodium conductance in skeletal muscle by intracellular and extracellular fatty acids

Wieland, Steven J.; Fletcher, Jeffrey E.; Gong, Qiong

doi:10.1152/ajpcell.1992.263.2.c308

Cited by 43 publications

(18 citation statements)

References 22 publications

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“…C2C12 cells showed typical skeletal muscle sodium currents ( Figure 2 and Table 1), as previously reported. 21 The time constants of decay ( h ) and recovery from inactivation are modestly but significantly slower in C2C12 cells compared with expressed 1 currents recorded under identical conditions (Table 1). In the absence of exogenous CaM, the steady-state availability of C2C12 Na ϩ currents is shifted ϷϪ20 mV compared with expressed 1 currents.…”

Section: Currents Recorded From C2c12 Cellsmentioning

confidence: 85%

“…17 C2C12 cells (American Type Culture Collection) are a subclone derived from a mouse myoblast cell line expressing characteristic muscle proteins. 21 Cells were grown in DMEM high glucose supplemented with FBS 10%, L-glutamine (2 mmol/L), penicillin (100 U/mL), and streptomycin (10 mg/mL) in a humidified 5% CO 2 atmosphere. Transfections of the cells were performed using lipofectamine according to the manufacturer's instructions.…”

Section: Transfections Of Hek293 and C2c12 Cell Linesmentioning

confidence: 99%

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Isoform-Specific Modulation of Voltage-Gated Na ⁺ Channels by Calmodulin

Deschênes

Neyroud

DiSilvestre

et al. 2002

Circulation Research

144

155

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Abstract-Calmodulin (CaM) is a calcium-sensing protein that binds to Na ϩ channels, with unknown functional consequences. Wild-type CaM produced a hyperpolarizing shift in the steady-state availability of expressed skeletal muscle (1) but not cardiac (hH1) Na ϩ channels. Mutant CaM 1234 did not alter the voltage dependence or the kinetics of gating of either 1 or hH1. Mutation of the highly conserved IQ motif in the carboxyl terminus of both isoforms (IQ/AA) slowed the kinetics of current decay and abolished the effect of wild-type CaM on 1, but did not alter hH1 currents. The IQ/AA mutation eliminated CaM binding to the carboxyl terminus of both 1 and hH1 channels. Inhibition of Ca 2ϩ /CaM kinase (CaM-K) slowed the current decay, the rate of entry into inactivation, and shifted the voltage dependence of hH1 in the depolarizing direction independent of CaM overexpression with no effect on 1 Na ϩ channels. CaM signaling modulates Na ϩ currents in an isoform-specific manner, via direct interaction with skeletal muscle Na ϩ channels and through CaM-K in the case of the cardiac isoform.

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Section: Currents Recorded From C2c12 Cellsmentioning

confidence: 85%

Section: Transfections Of Hek293 and C2c12 Cell Linesmentioning

confidence: 99%

Isoform-Specific Modulation of Voltage-Gated Na ⁺ Channels by Calmodulin

Deschênes

Neyroud

DiSilvestre

et al. 2002

Circulation Research

144

155

View full text Add to dashboard Cite

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“…muscle (7,33,49,52,59). Moreover, C 2 C 12 cells exhibit developmental regulation in the expression of voltage-gated ion channels much like they do in vivo and show TTXsensitive Na ϩ currents indicating the expression of Na v 1.4 (7,11,29,60). Spherically shaped, differentiated cells (myoballs) were selected for the electrophysiological experiments.…”

Section: A-23187 Treatment Causes Fast-to-slow Fiber Type Conversionmentioning

confidence: 99%

Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C₂C₁₂ skeletal muscle cells

Zebedin

Sandtner²,

Galler³

et al. 2004

American Journal of Physiology-Cell Physiology

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. Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C2C12 skeletal muscle cells. Am J Physiol Cell Physiol 287: C270 -C280, 2004. First published March 24, 2004 10.1152/ ajpcell.00015.2004.-Each skeletal muscle of the body contains a unique composition of "fast" and "slow" muscle fibers, each of which is specialized for certain challenges. This composition is not static, and the muscle fibers are capable of adapting their molecular composition by altered gene expression (i.e., fiber type conversion). Whereas changes in the expression of contractile proteins and metabolic enzymes in the course of fiber type conversion are well described, little is known about possible adaptations in the electrophysiological properties of skeletal muscle cells. Such adaptations may involve changes in the expression and/or function of ion channels. In this study, we investigated the effects of fast-to-slow fiber type conversion on currents via voltage-gated Na ϩ channels in the C2C12 murine skeletal muscle cell line. Prolonged treatment of cells with 25 nM of the Ca 2ϩ ionophore A-23187 caused a significant shift in myosin heavy chain isoform expression from the fast toward the slow isoform, indicating fast-to-slow fiber type conversion. Moreover, Na ϩ current inactivation was significantly altered. Slow inactivation less strongly inhibited the Na ϩ currents of fast-to-slow fiber type-converted cells. Compared with control cells, the Na ϩ currents of converted cells were more resistant to block by tetrodotoxin, suggesting enhanced relative expression of the cardiac Na ϩ channel isoform Nav1.5 compared with the skeletal muscle isoform Na v1.4. These results imply that fast-toslow fiber type conversion of skeletal muscle cells involves functional adaptation of their electrophysiological properties. muscle plasticity; myosin heavy chain expression; sodium channel expression ADULT SKELETAL MUSCLE has a remarkable capacity to adapt in response to altered functional demands such as enhanced activity or disuse. On the basis of contraction kinetics, a distinction is drawn between "fast" and "slow" skeletal muscles, which contain predominantly fast-and slow-type muscle fibers, respectively. These fiber types express specific sets of fast and slow protein isoforms (for review, see Refs. 5,36,47) and are generally categorized according to the specific myosin heavy chain (MHC) isoforms that they express. In adaptation to altered functional demands, muscle fibers can switch from the fast to the slow fiber type and vice versa (i.e., fiber type conversion). Fiber type conversion involves morphological and biochemical changes that result in altered contractile properties and endurance capacities. It is well established that motor neuron firing patterns control the expression of isoforms of contractile proteins and metabolic enzymes of muscle fibers in vivo (6, 44). These firing patterns have been mimicked successfully in vitro in cell culture studies by imposed electrical stimulation (28, 58). The cellular s...

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“…Skeletal muscle sodium channels can be either activated or inhibited by fatty acid exposure. The response is dependent on fatty acid structure, channel isotype, and extracellular versus cytoplasmic delivery (3). Skeletal muscle expresses a tetrodotoxin (TTX)-sensitive (SkM1) sodium channel and, when immature or denervated, a TTX-insensitive (SkM2) sodium channel (4).…”

mentioning

confidence: 99%

“…Skeletal muscle expresses a tetrodotoxin (TTX)-sensitive (SkM1) sodium channel and, when immature or denervated, a TTX-insensitive (SkM2) sodium channel (4). Differences in the effects of fatty acids on channel function appear to segregate between these two channel subtypes (3). We set out to analyze the separate responses to fatty acid exposure of the two subtypes by transiently expressing each type individually in a cell line.…”

mentioning

confidence: 99%

Modulation of Human Muscle Sodium Channels by Intracellular Fatty Acids Is Dependent on the Channel Isoform

Wieland

Gong

Poblete

et al. 1996

Journal of Biological Chemistry

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Free fatty acids (FFAs), including arachidonic acid (AA), are implicated in the direct and indirect modulation of a spectrum of voltage-gated ion channels. Skeletal muscle sodium channels can be either activated or inhibited by FFA exposure; the response is dependent on both FFA structure and site of exposure. Recombinant human skeletal muscle sodium channels (hSkM1) were transfected into heterologous human renal epithelium HEK293t cells. Cytoplasmic delivery of 5 M AA augmented the voltage-activated sodium current of hSkM1 channels by 190% (؎54 S.E., n ‫؍‬ 7) over a 20-min period. Similar results were seen with 5 M oleic acid. Sodium currents in HEK293t cells transfected with human cardiac muscle sodium channels (hH1) were insensitive to AA treatment, and exposure to oleic acid inhibited the hH1 currents over a 20-min period by 29% (؎13 S.E., n ‫؍‬ 5). The increase in hSkM1 current was not accompanied by shifts in voltage dependence of activation, steady-state inactivation, or markedly altered kinetics of inactivation of the macroscopic current. The FFA-induced increase in sodium currents was not dependent on protein kinase C activity. In contrast, both isoforms were reversibly inhibited by external application of unsaturated FFA. Thus, the differential effects of FFA on skeletal muscle sodium channels first noted in cultured muscle cells can be reproduced by expressing recombinant sodium channels in epithelial cells. Although the responses to applied FFAs could be direct or indirect, we suggest that: 1) SkM1 has two classes of response to FFA, one which produces augmentation of macroscopic currents with intracellular FFA, and a second which produces inhibition with extracellular FFA; 2) H1 has only one class of response, which produces inhibition with extracellular FFA. A testable hypothesis is that the presence or absence of each response is due to a specific structure in SkM1 or H1. These specific structures may directly interact with FFA or may interact with intermediate components.

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Differential modulation of a sodium conductance in skeletal muscle by intracellular and extracellular fatty acids

Cited by 43 publications

References 22 publications

Isoform-Specific Modulation of Voltage-Gated Na ⁺ Channels by Calmodulin

Isoform-Specific Modulation of Voltage-Gated Na ⁺ Channels by Calmodulin

Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C₂C₁₂ skeletal muscle cells

Modulation of Human Muscle Sodium Channels by Intracellular Fatty Acids Is Dependent on the Channel Isoform

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Differential modulation of a sodium conductance in skeletal muscle by intracellular and extracellular fatty acids

Cited by 43 publications

References 22 publications

Isoform-Specific Modulation of Voltage-Gated Na + Channels by Calmodulin

Isoform-Specific Modulation of Voltage-Gated Na + Channels by Calmodulin

Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C2C12 skeletal muscle cells

Modulation of Human Muscle Sodium Channels by Intracellular Fatty Acids Is Dependent on the Channel Isoform

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Isoform-Specific Modulation of Voltage-Gated Na ⁺ Channels by Calmodulin

Isoform-Specific Modulation of Voltage-Gated Na ⁺ Channels by Calmodulin

Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C₂C₁₂ skeletal muscle cells