A Cytoskeletal Mechanism for Ca2+ Channel Metabolic Dependence and Inactivation by Intracellular Ca2+

Johnson, Barry D.; Byerly, L

doi:10.1016/0896-6273(93)90196-x

Cited by 217 publications

(129 citation statements)

References 42 publications

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“…The cytoskeleton has been shown previously to regulate neuronal (20,22) and cardiac (21) Ca V 1.2 channels, and regulation of the Ca V 1 family of channels by PKA has been demonstrated in many different systems (41,42). Our results extend these findings by demonstrating functional effects of the cytoskeleton on the skeletal muscle Ca 2ϩ channel and interaction of those functional effects with regulation by PKA.…”

Section: Effects Of Pka On Voltage Dependence Of Ca 2؉ Channel Activisupporting

confidence: 75%

“…The actin cytoskeleton affects multiple ion channels, including voltage-gated Na ϩ channels (17)(18)(19), Ca 2ϩ channels (19)(20)(21)(22), K ϩ channels (23,24), Cl Ϫ channels (25)(26)(27)(28), amiloride-sensitive epithelial Na ϩ channels (26,29,30), mechanosensitive Na ϩ channels (31), GABA A receptors (32), and glutamate receptors (33,34). The cytoskeleton is composed of the following three primary types of filaments: microfilaments composed of actin monomers, intermediate filaments composed of intermediate filament proteins, and microtubules composed of ␣-and ␤-tubulin dimers.…”

mentioning

confidence: 99%

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Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Johnson

Scheuer

Catterall

2005

Proc. Natl. Acad. Sci. U.S.A.

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The skeletal muscle L-type Ca 2؉ channel (CaV1.1), which is responsible for initiating muscle contraction, is regulated by phosphorylation by cAMP-dependent protein kinase (PKA) in a voltagedependent manner that requires direct physical association between the channel and the kinase mediated through A-kinase anchoring proteins (AKAPs). The role of the actin cytoskeleton in channel regulation was investigated in skeletal myocytes cultured from wild-type mice, mdx mice that lack the cytoskeletal linkage protein dystrophin, and a skeletal muscle cell line, 129 CB 3. Voltage dependence of channel activation was shifted positively, and potentiation was greatly diminished in mdx myocytes and in 129 CB 3 cells treated with the microfilament stabilizer phalloidin. Voltage-dependent potentiation by strong depolarizing prepulses was reduced in mdx myocytes but could be restored by positively shifting the stimulus potentials to compensate for the positive shift in the voltage dependence of gating. Inclusion of PKA in the pipette caused a negative shift in the voltage dependence of activation and restored voltage-dependent potentiation in mdx myocytes. These results show that skeletal muscle Ca 2؉ channel activity and voltage-dependent potentiation are controlled by PKA and microfilaments in a convergent manner. Regulation of Ca 2؉ channel activity by hormones and neurotransmitters that use the PKA signal transduction pathway may interact in a critical way with the cytoskeleton and may be impaired by deletion of dystrophin, contributing to abnormal regulation of intracellular calcium concentrations in dystrophic muscle.calcium channel ͉ protein phosphorylation ͉ muscular dystrophy V oltage-gated Ca 2ϩ channels present in most cells play a critical role in converting cellular electrical activity into an intracellular Ca 2ϩ signal. Neurotransmitter and hormone release from neurons and endocrine cells, gene expression in many cell types, and contraction of cardiac, smooth, and skeletal muscle are all dependent on the activity of voltage-gated Ca 2ϩ channels. In skeletal muscle cells, the Ca V 1.1 channels in transverse tubules have two distinct functional roles. They serve as the voltage sensor for excitation-contraction coupling and transduce a voltage-dependent conformational change into activation of the ryanodine-sensitive Ca 2ϩ release channels in the sarcoplasmic reticulum (1, 2). Ca 2ϩ release from the sarcoplasmic reticulum rapidly initiates contraction. In addition, on a slower time scale, the L-type Ca 2ϩ current conducted by these channels is activated, and the resulting Ca 2ϩ influx increases contractile force in subsequent contractions (3, 4) and regulates gene expression and other muscle activities (5).Activation of skeletal muscle Ca 2ϩ channels is increased by cAMP-dependent phosphorylation in response to adrenergic stimulation (3, 6) and is further potentiated by strong depolarization (7-9), which requires cAMP-dependent protein kinase (PKA) phosphorylation (7). PKA is often anchored near substrates by A-kinas...

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Section: Effects Of Pka On Voltage Dependence Of Ca 2؉ Channel Activisupporting

confidence: 75%

mentioning

confidence: 99%

Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Johnson

Scheuer

Catterall

2005

Proc. Natl. Acad. Sci. U.S.A.

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“…5C). As expected from previous studies (Johnson and Byerly, 1993;Rosenmund and Westbrook, 1993), cytochalasin D accelerated the rate of rundown of currents through both V DCC and NMDA receptors but did not affect kainate-induced currents (data not shown). When taken together with the calcium imaging data, our patch-clamp data indicate that, by inducing actin depolymerization, gelsolin acts to suppress C a 2ϩ influx through VDCC and NMDA receptors.…”

Section: Reduced Rundown Of Voltage-dependent Calcium Current and Nmdsupporting

confidence: 70%

“…The enhanced response to glutamate was likely the result of decreased actin depolymerization in the GϪ/Ϫ neurons, rather than some other consequence of absence of gelsolin, because the effect was abolished in GϪ/Ϫ neurons treated with the actin-depolymerizing agent cytochalasin D. Previous whole-cell patch-clamp analyses in which actin depolymerization in cultured neurons was induced by pharmacological treatment with cytochalasin D provided evidence that F-actin promotes prolonged opening of NMDA receptor channels (Rosenmund and Westbrook, 1993) and VDCC (Johnson and Byerly, 1993). Our data indicate that calciuminduced, gelsolin-mediated actin depolymerization resulting from physiological stimuli (membrane depolarization and glutamate) promotes rapid rundown of NMDA current and calcium current.…”

Section: Discussionmentioning

confidence: 99%

“…Recent findings suggest that, in addition to their roles in regulating cell structure and motility, actin filaments may f unction in the modulation of ion channel f unction. The evidence is based on pharmacological data showing that the actin filament-disrupting agent cytochalasin D can alter ion flux through Na ϩ channels (C antiello et al, 1991;Undrovinas et al, 1995;Berdiev et al, 1996), voltage-dependent calcium channels (VDCC) (Johnson and Byerly, 1993), and NMDA receptor channels (Rosenmund and Westbrook, 1993). Whether actin normally plays roles in regulating Ca 2ϩ influx in physiological and pathophysiological settings is unknown.…”

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confidence: 99%

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The Actin-Severing Protein Gelsolin Modulates Calcium Channel and NMDA Receptor Activities and Vulnerability to Excitotoxicity in Hippocampal Neurons

et al. 1997

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Calcium influx through NMDA receptors and voltagedependent calcium channels (VDCC) mediates an array of physiological processes in neurons and may also contribute to neuronal degeneration and death in neurodegenerative conditions such as stroke and severe epileptic seizures. Gelsolin is a Ca 2ϩ -activated actin-severing protein that is expressed in neurons, wherein it may mediate motility responses to Ca 2ϩ influx. Primary hippocampal neurons cultured from mice lacking gelsolin exhibited decreased actin filament depolymerization and enhanced Ca 2ϩ influx after exposure to glutamate. Whole-cell patch-clamp analyses showed that currents through NMDA receptors and VDCC were enhanced in hippocampal neurons lacking gelsolin, as a result of decreased current rundown; kainate-induced currents were similar in neurons containing and lacking gelsolin. Vulnerability of cultured hippocampal neurons to glutamate toxicity was greater in cells lacking gelsolin. Seizure-induced damage to hippocampal pyramidal neurons was exacerbated in adult gelsolin-deficient mice. These findings identify novel roles for gelsolin in controlling actinmediated feedback regulation of Ca 2ϩ influx and in neuronal injury responses. The data further suggest roles for gelsolin and the actin cytoskeleton in both physiological and pathophysiological events that involve activation of NMDA receptors and VDCC.

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Rapid regulation of cytoskeletal proteins and their mRNAs following afferent deprivation in the avian cochlear nucleus

1997

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During development, removal of neuronal input can lead to profound changes in postsynaptic cells, including atrophy and cell death. In the chicken brainstem cochlear nucleus, the nucleus magnocellularis (NM), deprivation of auditory input via unilateral cochlea removal or silencing the eighth nerve with tetrodotoxin leads to a loss of 25-30% of the neurons and the atrophy of surviving neurons. One intracellular component that may be involved in both cell atrophy and cell death is the cytoskeleton. The degradation of the cytoskeleton following deafferentation could potentially lead to either atrophy or death of NM neurons. However, little is known regarding the role of neuronal input on the cytoskeletal structure of NM neurons and whether changes in the cytoskeleton are responsible for cell death following deafferentation. The present study examined whether changes in the cytoskeleton of NM neurons occurred following cochlea removal. Several components of the cytoskeleton were analyzed following unilateral afferent deprivation. Levels of immunostaining for tubulin, actin, and microtubule-associated protein 2 (MAP-2), and levels of beta-tubulin and beta-actin mRNAs were assessed in NM neurons following cochlea removal. Our results revealed that afferent deprivation results in a rapid decrease in immunostaining for all three cytoskeletal proteins examined. These decreases were observed as early as 3 hours after cochlea removal and persisted for up to 4 days. In addition, these changes occurred in all deafferented NM neurons at the early time points, indicating that both dying and surviving NM neurons undergo a similar change in their cytoskeletons. In contrast to the decreases in immunostaining, levels of beta-tubulin and beta-actin mRNAs were not noticeably altered by deafferentation. Our findings indicate that the cytoskeleton is altered or degraded following deafferentation but that this process is not regulated at the transcriptional level.

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A Cytoskeletal Mechanism for Ca2+ Channel Metabolic Dependence and Inactivation by Intracellular Ca2+

Cited by 217 publications

References 42 publications

Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

The Actin-Severing Protein Gelsolin Modulates Calcium Channel and NMDA Receptor Activities and Vulnerability to Excitotoxicity in Hippocampal Neurons

Rapid regulation of cytoskeletal proteins and their mRNAs following afferent deprivation in the avian cochlear nucleus

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A Cytoskeletal Mechanism for Ca2+ Channel Metabolic Dependence and Inactivation by Intracellular Ca2+

Cited by 217 publications

References 42 publications

Convergent regulation of skeletal muscle Ca 2+ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Convergent regulation of skeletal muscle Ca 2+ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

The Actin-Severing Protein Gelsolin Modulates Calcium Channel and NMDA Receptor Activities and Vulnerability to Excitotoxicity in Hippocampal Neurons

Rapid regulation of cytoskeletal proteins and their mRNAs following afferent deprivation in the avian cochlear nucleus

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Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase