scholarly journals Effect of Verapamil, an L-Type Calcium Channel Inhibitor, on Caveolin-3 Expression in Septic Mouse Hearts

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Bruna A. C. Rattis ◽  
Ana C. Freitas ◽  
Jordana F. Oliveira ◽  
João L. A. Calandrini-Lima ◽  
Maria J. Figueiredo ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Homeostasis ◽  
Myocardial Dysfunction ◽  
Vital Role ◽  
Cardiac Cells ◽  
Structural Protein ◽  
Cardiac Muscle Cells ◽  
Septic Mouse ◽  
Cardiac Lesions

Sepsis-induced myocardial dysfunction considerably increases mortality risk in patients with sepsis. Previous studies from our group have shown that sepsis alters the expression of structural proteins in cardiac cells, resulting in cardiomyocyte degeneration and impaired communication between cardiac cells. Caveolin-3 (CAV3) is a structural protein present in caveolae, located in the membrane of cardiac muscle cells, which regulates physiological processes such as calcium homeostasis. In sepsis, there is a disruption of calcium homeostasis, which increases the concentration of intracellular calcium, which can lead to the activation of potent cellular enzymes/proteases which cause severe cellular injury and death. The purpose of the present study was to test the hypotheses that sepsis induces CAV3 overexpression in the heart, and the regulation of L-type calcium channels directly relates to the regulation of CAV3 expression. Severe sepsis increases the expression of CAV3 in the heart, as immunostaining in our study showed CAV3 presence in the cardiomyocyte membrane and cytoplasm, in comparison with our control groups (without sepsis) that showed CAV3 presence predominantly in the plasma membrane. The administration of verapamil, an L-type calcium channel inhibitor, resulted in a decrease in mortality rates of septic mice. This effect was accompanied by a reduction in the expression of CAV3 and attenuation of cardiac lesions in septic mice treated with verapamil. Our results indicate that CAV3 has a vital role in cardiac dysfunction development in sepsis and that the regulation of L-type calcium channels may be related to its expression.

Regulation of calcium transport in cardiac cells

1984 ◽  
Vol 62 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Adil E. Shamoo ◽  
Indu S. Ambudkar
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Channel ◽  
Calcium Homeostasis ◽  
Calcium Transport ◽  
Cardiac Cells ◽  
Transport Systems ◽  
Sodium Calcium Exchanger ◽  
Inotropic Effects ◽  
Cellular Calcium ◽  
Sodium Calcium

Calcium transporting systems and the regulatory events accompanying them are pivotal in the function of the cardiac cell. The concerted involvement of the various membranes achieve cellular calcium homeostasis that can also respond to the physiological exigencies of the cell. Three membrane systems are primarily involved; the sarcolemma, sarcoplasmic reticulum, and the mitochondria. The various Ca2+ transport systems that have been described in these membranes are as follows: the calcium channel, Ca2+-ATPase, Ca2+–Mg2+ ATPase, and sodium–calcium exchanger in the sarcolemma; the Ca2+–Mg2+ ATPase and a possible calcium channel in the sarcoplasmic reticulum; and the sodium–calcium exchanger and electrophoretic calcium uniporter in the mitochondrial inner membrane. These systems mediate calcium fluxes to maintain physiological cytosolic calcium concentrations. β-Adrenergic hormones regulate calcium transport systems in sarcolemma and sarcoplasmic reticulum, while α-adrenergic hormones modulate those in the mitochondria and probably in the sarcolemma. The response to these hormones is initiated at the sarcolemma, which contains the specific receptors. Intracellularly the effects are propagated by secondary messengers, e.g., cAMP, calcium, and lipid changes. Specific proteins are also involved in these events. Phospholamban, a 22 000 dalton protein, is involved in mediating the cAMP-dependent inotropic effects, by activating the Ca2+–Mg2+ ATPase of the sarcoplasmic reticulum. Alterations in any one of the systems involved in the regulation of calcium transport or in the calcium transport systems per se, would then result in drastic alterations in the cellular calcium homeostasis. Such effects could be of significance in cellular dysfunction during cardiac disease.

scholarly journals Properties and modulation of cardiac calcium channels

1986 ◽  
Vol 124 (1) ◽  
pp. 191-201 ◽  
Author(s):  
H. Reuter ◽  
S. Kokubun ◽  
B. Prod'hom
Keyword(s):  
Cyclic Amp ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Cardiac Cells ◽  
Cellular Functions ◽  
Beta Adrenoceptor ◽  
Excitable Membranes ◽  
Rat Hearts ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

Voltage-dependent calcium channels are widely distributed in excitable membranes and are involved in the regulation of many cellular functions. These channels can be modulated by neurotransmitters and drugs. There is one particular type of calcium channel in cardiac cells (L-type) whose gating is affected in different ways by beta-adrenoceptor and 1,4-dihydropyridine agonists. We have analysed single calcium channel currents (i) in myocytes from rat hearts in the absence and presence of isoproterenol or 8-bromo-cAMP. We have found that both compounds have similar effects on calcium channel properties. They increase the overall open state probability (po) of individual calcium channels while i remains unaffected. Analysis of the gating kinetics of calcium channels showed: a slight increase in the mean open times of calcium channels, a reduction in time intervals between bursts of channel openings, an increase in burst length and a prominent reduction in failures of calcium channels to open upon depolarization. These kinetic changes caused by isoproterenol and 8-bromo-cAMP can account for the increase in po. Since the macroscopic calcium current, ICa, can be described by ICa = N X po X i, the increase in po accounts for the well-known increase in ICa by beta-adrenergic catecholamines. Cyclic AMP-dependent phosphorylation of calcium channels is a likely metabolic step involved in this modulation. Another class of drug that modulates calcium channel gating is the 1,4-dihydropyridines which can either enhance or reduce ICa, either by prolonging the open state of the channels or by facilitating the inactivated state. Both effects depend strongly on membrane potential and are independent of cyclic AMP-dependent phosphorylation reactions.

scholarly journals A Dihydropyridine-sensitive Voltage-dependent Calcium Channel in the Sarcolemmal Membrane of Crustacean Muscle

1997 ◽  
Vol 109 (3) ◽  
pp. 313-326 ◽  
Author(s):  
Christian Erxleben ◽  
Werner Rathmayer
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Single Channel ◽  
Resting Membrane Potential ◽  
Open Probability ◽  
Cardiac Muscle Cells ◽  
Idotea Baltica ◽  
Voltage Dependent ◽  
Marine Crustacean ◽  
Single Channel Currents

Single-channel currents through calcium channels in muscle of a marine crustacean, the isopod Idotea baltica, were investigated in cell-attached patches. Inward barium currents were strongly voltage-dependent, and the channels were closed at the cell's resting membrane potential. The open probability (Po) increased e-fold for an 8.2 mV (±2.4, n = 13) depolarization. Channel openings were mainly brief (<0.3 ms) and evenly distributed throughout 100-ms pulses. Averaged, quasimacroscopic currents showed fast activation and deactivation and did not inactivate during 100-ms test pulses. Similarly, channel activity persisted at steadily depolarized holding potentials. With 200 mM Ba2+ as charge carrier, the average slope conductance from the unitary currents between +30 and +80 mV, was 20 pS (±2.6, n = 12). The proportion of long openings, which were very infrequent under control conditions, was greatly increased by preincubation of the muscle fibers with the calcium channel agonist, the dihydropyridine Bay K8644 (10–100 μM). Properties of these currents resemble those through the L-type calcium channels of mammalian nerve, smooth muscle, and cardiac muscle cells.

scholarly journals Caenorhabditis elegans Junctophilin has tissue-specific functions and regulates neurotransmission with extended-synaptotagmin

Genetics ◽  
2021 ◽  
Author(s):  
Christopher A Piggott ◽  
Zilu Wu ◽  
Stephen Nurrish ◽  
Suhong Xu ◽  
Joshua M Kaplan ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Tissue Specific ◽  
Voltage Gated ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Pharyngeal Muscles ◽  
Membrane Contact ◽  
Null Mutants

Abstract The junctophilin family of proteins tether together plasma membrane (PM) and endoplasmic reticulum (ER) membranes, and couple PM- and ER-localized calcium channels. Understanding in vivo functions of junctophilins is of great interest for dissecting the physiological roles of ER-PM contact sites. Here, we show that the sole C. elegans junctophilin JPH-1 localizes to discrete membrane contact sites in neurons and muscles and has important tissue-specific functions. jph-1 null mutants display slow growth and development due to weaker contraction of pharyngeal muscles, leading to reduced feeding. In the body wall muscle, JPH-1 co-localizes with the PM-localized EGL-19 voltage-gated calcium channel and ER-localized UNC-68/RyR calcium channel, and is required for animal movement. In neurons, JPH-1 co-localizes with the membrane contact site protein Extended-SYnaptoTagmin 2 (ESYT-2) in soma, and is present near presynaptic release sites. Interestingly, jph-1 and esyt-2 null mutants display mutual suppression in their response to aldicarb, suggesting that JPH-1 and ESYT-2 have antagonistic roles in neuromuscular synaptic transmission. Additionally, we find an unexpected cell non-autonomous effect of jph-1 in axon regrowth after injury. Genetic double mutant analysis suggests that jph-1 functions in overlapping pathways with two PM-localized voltage-gated calcium channels, egl-19 and unc-2, and unc-68/RyR for animal health and development. Finally, we show that jph-1 regulates the colocalization of EGL-19 and UNC-68 and that unc-68/RyR is required for JPH-1 localization to ER-PM puncta. Our data demonstrate important roles for junctophilin in cellular physiology, and also provide insights into how junctophilin functions together with other calcium channels in vivo.

scholarly journals Voltage-gated calcium channel blockers for psychiatric disorders: genomic reappraisal

2019 ◽  
Vol 216 (5) ◽  
pp. 250-253 ◽  
Author(s):  
Paul J. Harrison ◽  
Elizabeth M. Tunbridge ◽  
Annette C. Dolphin ◽  
Jeremy Hall
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Psychiatric Disorders ◽  
Calcium Channel Blockers ◽  
Channel Blockers ◽  
Risk Genes ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Voltage Gated Calcium Channel ◽  
Second Use

SummaryWe reappraise the psychiatric potential of calcium channel blockers (CCBs). First, voltage-gated calcium channels are risk genes for several disorders. Second, use of CCBs is associated with altered psychiatric risks and outcomes. Third, research shows there is an opportunity for brain-selective CCBs, which are better suited to psychiatric indications.

scholarly journals Courtship and Visual Defects of cacophony Mutants Reveal Functional Complexity of a Calcium-Channel α1 Subunit in Drosophila

Genetics ◽  
1998 ◽  
Vol 149 (3) ◽  
pp. 1407-1426 ◽  
Author(s):  
Lee A Smith ◽  
Alexandre A Peixoto ◽  
Elena M Kramer ◽  
Adriana Villella ◽  
Jeffrey C Hall
Keyword(s):  
Alternative Splicing ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Stop Codon ◽  
Biological Functions ◽  
Visual Defects ◽  
Transcript Diversity ◽  
Functional Complexity ◽  
Α1 Subunit ◽  
Subtle Abnormality

Abstract We show by molecular analysis of behavioral and physiological mutants that the Drosophila Dmca1A calcium-channel α1 subunit is encoded by the cacophony (cac) gene and that nightblind-A and lethal(1)L13 mutations are allelic to cac with respect to an expanded array of behavioral and physiological phenotypes associated with this gene. The cacS mutant, which exhibits defects in the patterning of courtship lovesong and a newly revealed but subtle abnormality in visual physiology, is mutated such that a highly conserved phenylalanine (in one of the quasi-homologous intrapolypeptide regions called IIIS6) is replaced by isoleucine. The cacH18 mutant exhibits defects in visual physiology (including complete unresponsiveness to light in certain genetic combinations) and visually mediated behaviors; this mutant (originally nbAH18) has a stop codon in an alternative exon (within the cac ORF), which is differentially expressed in the eye. Analysis ofthe various courtship and visual phenotypes associated with this array ofcac mutants demonstrates that Dmca1A calcium channels mediate multiple, separable biological functions; these correlate in part with transcript diversity generated via alternative splicing.

Role of calcium channels and protein kinase C for release of norepinephrine and neuropeptide Y

1990 ◽  
Vol 259 (5) ◽  
pp. R925-R930
Author(s):  
M. Haass ◽  
C. Forster ◽  
G. Richardt ◽  
R. Kranzhofer ◽  
A. Schomig
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Neuropeptide Y ◽  
Nerve Fibers ◽  
Extracellular Calcium ◽  
Minor Effect ◽  
Kinase C

The role of calcium for the release of norepinephrine (NE, determined by high-pressure liquid chromatography) and neuropeptide Y (NPY, determined by radioimmunoassay) was investigated in guinea pig perfused hearts with intact sympathetic innervation. In the presence of extracellular calcium (1.85 mM), electrical stimulation of the left stellate ganglion (12 Hz, 1 min) induced a closely related release of NE and NPY with the molar ratio of approximately 400-600 (NE) to 1 (NPY). The stimulation-evoked overflow of both transmitters was dependent from the extracellular calcium concentration and was almost completely suppressed by calcium-free perfusion. The corelease of both transmitters was not affected by the L-type calcium channel blocker felodipine (1-10 microM). However, the overflow of NE and NPY was markedly attenuated by the unselective calcium antagonist flunarizine (1-10 microM) and completely prevented by the neuronal (N-type) calcium channel blockers omega-conotoxin (1-100 nM) and cadmium chloride (10-100 microM), indicating a key role for N-type calcium channels in the exocytotic release of transmitters from cardiac sympathetic nerve fibers. Possibly due to unspecific actions, such as interference with sodium channels or uptake1-blocking properties, the phenylalkylamines verapamil (0.01-10 microM) and gallopamil (1-10 microM) reduced NPY overflow with only a minor effect on NE overflow. The stimulation-induced transmitter release was increased up to twofold by activation of protein kinase C (phorbol 12-myristate 13-acetate, 3 nM-3 microM) and completely suppressed by inhibition of protein kinase C (polymyxin B, 100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Expression of a developmentally regulated antigen on the surface of skeletal and cardiac muscle cells.

1985 ◽  
Vol 100 (6) ◽  
pp. 1977-1987 ◽  
Author(s):  
S J Kaufman ◽  
R F Foster ◽  
K R Haye ◽  
L E Faiman
Keyword(s):  
Cell Surface ◽  
Cardiac Muscle ◽  
Surface Antigen ◽  
Cardiac Cells ◽  
Cell Surface Antigen ◽  
Myoblast Differentiation ◽  
Specific Cell ◽  
Developmentally Regulated ◽  
Cardiac Muscle Cells ◽  
Species Specific

H36 is a species-specific, cell-surface antigen on differentiating newborn rat skeletal myoblasts and myogenic lines. This membrane antigen has been defined by a monoclonal antibody raised by the fusion of SP 2/0-Ag14 myeloma cells with spleen cells from mice immunized with myotubes derived from the myogenic E63 line. H36 antigen, isolated by immunoaffinity chromatography, is comprised of two polypeptides with apparent molecular weights of 98,000 and 117,000. Fluorescence photometry and radioimmunoassays have been used to follow quantitative and topographic changes in the H36 determinant during myogenesis. H36 is present at a basal level on replicating myoblasts; it increases on prefusion myoblasts and persists on myotubes. At or near the time of prefusion, it becomes concentrated between adjacent aligned myoblasts and localized on membrane "blebs". H36 is present on both skeletal and cardiac cells but absent from a variety of cells that include fibroblasts, neuronal cells, and smooth muscle. There are approximately 4 x 10(5) determinants per myoblast, and the Ka of the antibody is 3.8 x 10(8) liters/mol. The distributions of H36 on the top and attached surfaces of myoblasts and myotubes are distinct, which suggests localized specialization of these surfaces. H36 is an integral membrane component and upon cross-linking, it associates with the detergent-insoluble cytoskeletal framework. Inhibition of myogenesis by 5-bromodeoxyuridine or by calcium deprivation prevents the developmentally associated changes in the expression of H36. H36 is also absent or markedly reduced on the fu- and Ama102 developmentally defective mutant myoblast lines. We conclude that H36 is a muscle-specific, developmentally regulated cell-surface antigen that may have a role in myoblast differentiation and that can be used to determine the embryonic lineages of skeletal and cardiac muscle.

scholarly journals Insulation of the conduction pathway of muscle transverse tubule calcium channels from the surface charge of bilayer phospholipid.

1986 ◽  
Vol 87 (6) ◽  
pp. 933-953 ◽  
Author(s):  
R Coronado ◽  
H Affolter
Keyword(s):  
Ionic Strength ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Surface Charge ◽  
Single Channel ◽  
Small Surface ◽  
Bilayer Lipid ◽  
Sodium Conductance ◽  
Conduction Pathway ◽  
Lipid Surface

Functional calcium channels present in purified skeletal muscle transverse tubules were inserted into planar phospholipid bilayers composed of the neutral lipid phosphatidylethanolamine (PE), the negatively charged lipid phosphatidylserine (PS), and mixtures of both. The lengthening of the mean open time and stabilization of single channel fluctuations under constant holding potentials was accomplished by the use of the agonist Bay K8644. It was found that the barium current carried through the channel saturates as a function of the BaCl2 concentration at a maximum current of 0.6 pA (at a holding potential of 0 mV) and a half-saturation value of 40 mM. Under saturation, the slope conductance of the channel is 20 pS at voltages more negative than -50 mV and 13 pS at a holding potential of 0 mV. At barium concentrations above and below the half-saturation point, the open channel currents were independent of the bilayer mole fraction of PS from XPS = 0 (pure PE) to XPS = 1.0 (pure PS). It is shown that in the absence of barium, the calcium channel transports sodium or potassium ions (P Na/PK = 1.4) at saturating rates higher than those for barium alone. The sodium conductance in pure PE bilayers saturates as a function of NaCl concentration, following a curve that can be described as a rectangular hyperbola with a half-saturation value of 200 mM and a maximum conductance of 68 pS (slope conductance at a holding potential of 0 mV). In pure PS bilayers, the sodium conductance is about twice that measured in PE at concentrations below 100 mM NaCl. The maximum channel conductance at high ionic strength is unaffected by the lipid charge. This effect at low ionic strength was analyzed according to J. Bell and C. Miller (1984. Biophysical Journal. 45:279-287) and interpreted as if the conduction pathway of the calcium channel were separated from the bilayer lipid by approximately 20 A. This distance thereby effectively insulates the ion entry to the channel from the bulk of the bilayer lipid surface charge. Current vs. voltage curves measured in NaCl in pure PE and pure PS show that similarly small surface charge effects are present in both inward and outward currents. This suggests that the same conduction insulation is present at both ends of the calcium channel.

Depolarization-stimulated cholecystokinin secretion is mediated by L-type calcium channels in STC-1 cells

1996 ◽  
Vol 270 (2) ◽  
pp. G287-G290 ◽  
Author(s):  
A. W. Mangel ◽  
L. Scott ◽  
R. A. Liddle
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Single Channel ◽  
Bay K 8644 ◽  
Ic50 Value ◽  
Single Channel Currents ◽  
Dose Dependent ◽  
Cck Release

To examine the role of calcium channels in depolarization-activated cholecystokinin (CCK) release, studies were performed in an intestinal CCK-secreting cell line, STC-1. Blockade of potassium channels with barium chloride (5 mM) increased the release of CCK by 374.6 +/- 46.6% of control levels. Barium-induced secretion was inhibited by the L-type calcium-channel blocker, nicardipine. Nicardipine (10(-9)-10(-5) M) produced a dose-dependent inhibition in barium-stimulated secretion with a half-maximal inhibition (IC50) value of 0.1 microM. A second L-type calcium-channel blocker, diltiazem (10(-9)-10(-4) M), also inhibited barium-induced CCK secretion with an IC50 value of 5.1 microM. By contrast, the T-type calcium-channel blocker, nickel chloride (10(-7)-10(-8) M), failed to significantly inhibit barium-induced CCK secretion. To further evaluate a role for L-type calcium channels in the secretion of CCK, the effects of the L-type calcium channel opener, BAY K 8644, were examined. BAY K 8644 (10(-8)-10(-4) M) produced a dose-dependent stimulation in CCK release with a mean effective concentration value of 0.2 microM. Recordings of single-channel currents from inside-out membrane patches showed activation of calcium channels by BAY K 8644 (1 microM), with a primary channel conductance of 26.0 +/- 1.2 pS. It is concluded that inhibition of potassium channel activity depolarizes the plasma membrane, thereby activating L-type, but not T-type, calcium channels. The corresponding influx of calcium serves to trigger secretion of CCK.

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