Sodium Channel in Human Malignant Hyperthermia

Fletcher, Jeffrey E.; Wieland, Steven J.; Karan, Steven M.; Beech, Jill; Rosenberg, Henry

doi:10.1097/00000542-199705000-00004

Cited by 18 publications

(25 citation statements)

References 36 publications

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“…Accordingly, in addition to being expressed in the heart, Na v 1.5 was originally thought to be expressed in embryonic and denervated, but not adult innervated, skeletal muscle (19,26,54). However, more recent studies (3,15) have provided strong evidence that Na v 1.5 is expressed and functions in normal innervated adult skeletal muscle as well. Thus Fletcher et al (15) detected significant Na v 1.5 mRNA levels by performing RT-PCR in vastus lateralis muscle biopsy specimens obtained from healthy humans.…”

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

confidence: 99%

“…However, more recent studies (3,15) have provided strong evidence that Na v 1.5 is expressed and functions in normal innervated adult skeletal muscle as well. Thus Fletcher et al (15) detected significant Na v 1.5 mRNA levels by performing RT-PCR in vastus lateralis muscle biopsy specimens obtained from healthy humans. The expression of Na v 1.5 was reduced ϳ20-fold in biopsy specimens obtained from patients susceptible to malignant hyperthermia, which resulted in a higher sensitivity of muscle twitches to TTX and thus had considerable functional consequences.…”

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

confidence: 99%

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

confidence: 99%

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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“…This is most likely achieved by an upregulation of expression of Na v 1.5 versus Na v 1.4 channels, both of which have previously been shown to be expressed in differentiated C 2 C 12 cells (49), as well as in adult innervated human skeletal muscle (9). The experiments were performed on mouse C 2 C 12 skeletal muscle cells, since these exhibit Fig.…”

Section: Discussionmentioning

confidence: 99%

C₂C₁₂ skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment

Zebedin¹,

Mille²,

Speiser³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Intracardiac transplantation of undifferentiated skeletal muscle cells (myoblasts) has emerged as a promising therapy for myocardial infarct repair and is already undergoing clinical trials. The fact that cells originating from skeletal muscle have different electrophysiological properties than cardiomyocytes, however, may considerably limit the success of this therapy and, in addition, cause side effects. Indeed, a major problem observed after myoblast transplantation is the occurrence of ventricular arrhythmias. The most often transient nature of these arrhythmias may suggest that, once transplanted into cardiac tissue, skeletal muscle cells adopt more cardiac-like electrophysiological properties. To test whether a cardiac cell environment can indeed modify electrophysiological parameters of skeletal muscle cells, we treated mouse C2C12 myocytes with medium preconditioned by primary cardiocytes and compared their functional sodium current properties with those of control cells. We found this treatment to significantly alter the activation and inactivation properties of sodium currents from “skeletal muscle” to more “cardiac”-like ones. Sodium currents of cardiac-conditioned cells showed a reduced sensitivity to block by tetrodotoxin. These findings and reverse transcription PCR experiments suggest that an upregulation of the expression of the cardiac sodium channel isoform Nav1.5 versus the skeletal muscle isoform Nav1.4 is responsible for the observed changes in sodium current function. We conclude that cardiomyocytes alter sodium channel isoform expression of skeletal muscle cells via a paracrine mechanism. Thereby, skeletal muscle cells with more cardiac-like sodium current properties are generated.

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“…The rigidity that is frequently seen during a fulminant MH episode is the result of the inability of the Ca 2+ pumps and transporters to reduce the unbound myoplasmic Ca 2+ below the contractile threshold 44,47 . Human malignant hyperthermia is a heterogeneous disorder, and the down-regulation of sodium channel subunit may be involved in the final common pathway through which mutations in any one of several proteins, including the ryanodine receptor, could render a person susceptible 48 . These changes would prolong the sodium current making the cell membrane depolarized for a longer time, increasing calcium release time period from the terminal cisternae.…”

Section: Pathophysiologymentioning

confidence: 99%

Malignant Hyperthermia in Liver Transplantation

Fernandes¹,

Marinho²,

Cavalcante³

2012

Liver Transplantation - Basic Issues

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Sodium Channel in Human Malignant Hyperthermia

Cited by 18 publications

References 36 publications

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

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

C₂C₁₂ skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment

Malignant Hyperthermia in Liver Transplantation

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Sodium Channel in Human Malignant Hyperthermia

Cited by 18 publications

References 36 publications

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

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

C2C12 skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment

Malignant Hyperthermia in Liver Transplantation

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

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

C₂C₁₂ skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment