Expression of a cardiac Ca2+-release channel isoform in mammalian brain

Mammalian brain possesses ryanodine-sensitive Ca2+ channels, which in muscle cells mediate rapid Ca2+ release from intracellular stores during excitation-contraction coupling. Analysis of bovine brain ryanodine receptor (RyR) channels suggests specific expression of the cardiac-muscle RyR isoform in mammalian brain. Localization using cardiac-muscle RyR-specific antibodies and antisense RNA revealed that brain RyRs were present in dendrites, cell bodies and terminals of rat forebrain, and highly enriched in the hippocampus. Activity of skeletal-muscle RyR channels is coupled to sarcolemmal voltage sensors, in contrast with cardiac-muscle RyR channels, which are known to be Ca(2+)-induced Ca(2+)-release channels. Thus Ca(2+)-induced Ca2+ release from intracellular stores mediated by brain RyR channels may be a major Ca(2+)-signalling pathway in specific regions of mammalian brain, and hence may play a fundamental role in neuronal Ca2+ homoeostasis.

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Cyclic adenosine 3':5'-monophosphate-dependent protein kinase. Comparison of type II enzymes from bovine brain, skeletal muscle, and cardiac muscle.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)32759-5 ◽

1983 ◽

Vol 258 (6) ◽

pp. 3950-3955

Author(s):

F T Hartl ◽

R Roskoski

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Cardiac Muscle ◽

Bovine Brain ◽

Type Ii ◽

Dependent Protein Kinase ◽

Dependent Protein

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Biphasic effects of doxorubicin on the calcium release channel from sarcoplasmic reticulum of cardiac muscle.

Circulation Research ◽

10.1161/01.res.67.5.1167 ◽

1990 ◽

Vol 67 (5) ◽

pp. 1167-1174 ◽

Cited By ~ 54

Author(s):

K Ondrias ◽

L Borgatta ◽

D H Kim ◽

B E Ehrlich

Keyword(s):

Sarcoplasmic Reticulum ◽

Cardiac Muscle ◽

Calcium Release ◽

Calcium Release Channel ◽

Release Channel

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Role of local Ca2+ domains in activation of Ca(2+)-induced Ca2+ release in crayfish muscle fibers

AJP Cell Physiology ◽

10.1152/ajpcell.1993.264.6.c1505 ◽

1993 ◽

Vol 264 (6) ◽

pp. C1505-C1512 ◽

Cited By ~ 21

Author(s):

S. Gyorke ◽

P. Palade

Keyword(s):

Sarcoplasmic Reticulum ◽

Cardiac Muscle ◽

Binding Site ◽

Equal Access ◽

Crayfish Muscle ◽

Simultaneous Measurements ◽

Indicator Analysis ◽

Dependent Processes ◽

Ca2 Channels

Simultaneous measurements were made of crayfish muscle Ca2+ currents (ICa) and the intracellular Ca2+ transients they elicit due to Ca(2+)-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR). Ca2+ concentration ([Ca2+]) elevations produced by Ca2+ entry via ICa were much more effective in triggering CICR than were ongoing release or homogeneous elevations of Ca2+ produced by photolysis of caged Ca2+. This suggests that [Ca2+] gradients exist when Ca2+ is elevated by ICa and that, during Ca2+ entry, [Ca2+] at the activation site of the release channels must be much greater than spatially averaged [Ca2+] reported by the indicator. Analysis of voltage dependencies of ICa inactivation and SR Ca2+ release suggest that both Ca(2+)-dependent processes are controlled by ICa via the nearest T tubule Ca2+ channel rather than by total ICa entry. The contribution of SR Ca2+ release to ICa inactivation studied with a two-pulse protocol was less than predicted if Ca2+ derived from SR Ca2+ release and from T tubule Ca2+ channels have equal access to the Ca2+ binding site controlling ICa inactivation. These results can be explained in terms of a scheme where sites for release activation and ICa inactivation are located in the same junctional gap subdomain, closer to the cytoplasmic mouth of the T tubule Ca2+ channel than to the cytoplasmic mouth of the SR Ca2+ release channels. Such a scheme could provide an explanation for the graded nature and selective control of CICR in this preparation as well as in vertebrate cardiac muscle.

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Interaction of Bupivacaine and Tetracaine with the Sarcoplasmic Reticulum Ca2+Release Channel of Skeletal and Cardiac Muscles

Anesthesiology ◽

10.1097/00000542-199903000-00027 ◽

1999 ◽

Vol 90 (3) ◽

pp. 835-843 ◽

Cited By ~ 45

Author(s):

Hirochika Komai ◽

Andrew J. Lokuta

Keyword(s):

Skeletal Muscle ◽

Sarcoplasmic Reticulum ◽

Cardiac Muscle ◽

Ryanodine Receptor ◽

Local Anesthetic ◽

Local Anesthetics ◽

Specific Effect ◽

Receptor Activity ◽

Maximal Inhibition ◽

Release Channel

Background Although various local anesthetics can cause histologic damage to skeletal muscle when injected intramuscularly, bupivacaine appears to have an exceptionally high rate of myotoxicity. Research has suggested that an effect of bupivacaine on sarcoplasmic reticulum Ca2+ release is involved in its myotoxicity, but direct evidence is lacking. Furthermore, it is not known whether the toxicity depends on the unique chemical characteristics of bupivacaine and whether the toxicity is found only in skeletal muscle. Methods The authors studied the effects of bupivacaine and the similarly lipid-soluble local anesthetic, tetracaine, on the Ca2+ release channel-ryanodine receptor of sarcoplasmic reticulum in swine skeletal and cardiac muscle. [3H]Ryanodine binding was used to measure the activity of the Ca2+ release channel-ryanodine receptors in microsomes of both muscles. Results Bupivacaine enhanced (by two times at 5 mM) and inhibited (66% inhibition at 10 mM) [3H]ryanodine binding to skeletal muscle microsomes. In contrast, only inhibitory effects were observed with cardiac microsomes (about 3 mM for half-maximal inhibition). Tetracaine, which inhibits [3H]ryanodine binding to skeletal muscle microsomes, also inhibited [3H]ryanodine binding to cardiac muscle microsomes (half-maximal inhibition at 99 microM). Conclusions Bupivacaine's ability to enhance Ca2+ release channel-ryanodine receptor activity of skeletal muscle sarcoplasmic reticulum most likely contributes to the myotoxicity of this local anesthetic. Thus, the pronounced myotoxicity of bupivacaine may be the result of this specific effect on Ca2+ release channel-ryanodine receptor superimposed on a nonspecific action on lipid bilayers to increase the Ca2+ permeability of sarcoplasmic reticulum membranes, an effect shared by all local anesthetics. The specific action of tetracaine to inhibit Ca2+ release channel-ryanodine receptor activity may in part counterbalance the nonspecific action, resulting in moderate myotoxicity.

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Epitranscriptomic Dysregulation in Stress-induced Psychopathologies

10.1101/2021.02.17.431575 ◽

2021 ◽

Author(s):

Dan Ohtan Wang ◽

Kandarp Joshi ◽

Anand Gururajan

Keyword(s):

Rna Stability ◽

Bioinformatic Analysis ◽

Fine Tuning ◽

Rna Modification ◽

Mammalian Brain ◽

Post Traumatic Stress ◽

Specific Expression ◽

Post Traumatic ◽

Transcriptional Gene Regulation ◽

Opening Up

AbstractTo date, over 100 different chemical modifications to RNA have been identified. Collectively known as the epitranscriptome, these modifications function to regulate RNA stability and as such, represent another mechanistic layer of post-transcriptional gene regulation. N6-methyladenosine (m6A) is the most common RNA modification in the mammalian brain and has been implicated in a number of processes relevant to neurodevelopment, brain function and behaviour. Here, following brief descriptions on epitranscriptomic mechanisms, we will review the literature on the potential functions of the m6A-methylome in fine-tuning gene expression which include prescribing localisation of transcripts in distal compartments as well as interactions with microRNAs and long non-coding RNAs. We will then discuss findings from rodent and human studies for stress-induced disorders - major depression and post-traumatic stress disorder – which support a hypothesis for a dysregulation of the m6A-methylome and the m6A-machinery in the pathophysiology. To support this, we have included a bioinformatic analysis of publicly available single-cell RNA-sequencing and bulk transcriptomics datasets which suggests an altered m6A-methylome as a consequence of dysregulated cell- and regionally-specific expression of key enzymes involved in the ‘writing, reading and erasing’ of m6A. We hope this review will generate further interest in the field of epitranscriptomics, opening up new lines of research into its involvement in psychiatric disorders.

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Transcription factor GATA-4 regulates cardiac muscle-specific expression of the alpha-myosin heavy-chain gene.

Molecular and Cellular Biology ◽

10.1128/mcb.14.7.4947 ◽

1994 ◽

Vol 14 (7) ◽

pp. 4947-4957 ◽

Cited By ~ 215

Author(s):

J D Molkentin ◽

D V Kalvakolanu ◽

B E Markham

Keyword(s):

Skeletal Muscle ◽

Transcription Factor ◽

Retinoic Acid ◽

Cardiac Muscle ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Binding Sites ◽

Ectopic Expression ◽

Specific Expression ◽

Cardiac Phenotype

The alpha-myosin heavy-chain (alpha-MHC) gene is the major structural protein in the adult rodent myocardium. Its expression is restricted to the heart by a complex interplay of trans-acting factors and their cis-acting sites. However, to date, the factors that have been shown to regulate expression of this gene have also been found in skeletal muscle cells. Recently, transcription factor GATA-4, which has a tissue distribution limited to the heart and endodermally derived tissues, was identified. We recently found two putative GATA-binding sites within the proximal enhancer of the alpha-MHC gene, suggesting that GATA-4 might regulate its expression. In this study, we establish that GATA-4 interacts with the alpha-MHC GATA sites to stimulate cardiac muscle-specific expression. Mutation of the GATA-4-binding sites either individually or together decreased activity by 50 and 88% in the adult myocardium, respectively. GATA-4-dependent enhancement of activity from a heterologous promoter was mediated through the alpha-MHC GATA sites. Coinjection of an alpha-MHC promoter construct with a GATA-4 expression vector permitted ectopic expression in skeletal muscle but not in fibroblasts. Thus, the lack of alpha-MHC expression in skeletal muscle correlates with a lack of GATA-4. GATA-4 DNA binding activity was significantly up-regulated in triiodothyronine- or retinoic acid-treated cardiomyocytes. Putative GATA-4-binding sites are also found in the regulatory regions of other cardiac muscle-expressed structural genes. This indicates a mechanism whereby triiodothyronine and retinoic acid can exert coordinate control of the cardiac phenotype through a trans-acting regulatory factor.

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Chapter 7: Nicotinic receptors in mammalian brain: localization and relation to cholinergic innervation

Cholinergic Function and Dysfunction - Progress in Brain Research ◽

10.1016/s0079-6123(08)62383-3 ◽

1993 ◽

pp. 77-83 ◽

Cited By ~ 52

Author(s):

Paul B.S. Clarke

Keyword(s):

Nicotinic Receptors ◽

Cholinergic Innervation ◽

Mammalian Brain ◽

Brain Localization

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Monoclonal antibodies against a C-terminal peptide of human brain acetylcholinesterase distinguish between erythrocyte and brain acetylcholinesterases

Clinical Chemistry ◽

10.1093/clinchem/42.1.19 ◽

1996 ◽

Vol 42 (1) ◽

pp. 19-23 ◽

Cited By ~ 4

Author(s):

N Boschetti ◽

U Brodbeck ◽

S P Jensen ◽

C Koch ◽

B Nørgaard-Pedersen

Keyword(s):

Monoclonal Antibodies ◽

Human Brain ◽

Solid Phase ◽

Bovine Brain ◽

Mammalian Brain ◽

Dot Blot ◽

Electric Eel ◽

Terminal Amino ◽

Dot Blot Analysis ◽

Brain Acetylcholinesterase

Abstract Monoclonal antibodies (mAbs) were raised against a peptide of the 10 C-terminal amino acids of human brain acetylcholinesterase (AChE): H-Tyr-Ser-Lys-Gln-Asp-Arg-Cys-Ser-Asp-Leu-OH. Two positive clones (mAbs 190-1 and 190-2) were selected and tested for their ability to distinguish between mammalian brain and erythrocyte AChEs. In a solid-phase enzyme antigen immunoassay as well as by Western- and dot-blot analysis, both antibodies showed clear binding to AChE from human and bovine brain but not to AChE from erythrocytes. MAbs 190-1 and 190-2 reacted with neither AChE from electric eel nor butyrylcholinesterase from human serum. Both antibodies were used in a quantitative assay for AChE in amniotic fluids, where AChE activity could be found only in samples from open neural tube-defect pregnancies, but not in fluids from normal pregnancies or in artificially blood-contaminated samples.

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