Protamine is a low molecular weight polycationic amine that produces actions on cardiac muscle

Pugsley, Michael K.; Kalra, VK; Froebel-Wilson, Sarah

doi:10.1016/s0024-3205(02)02245-2

Cited by 22 publications

(9 citation statements)

References 28 publications

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“…As previously reported for RyR1 [24], we observed full block of RyR2 in the presence of 20 µg/ml protamine. Addition of heparin (250 µg/ml), known to bind protamine with very high affinity [30], [31], [32], reversed the effect of protamine on RyR2. This reversibility suggests that the action of protamine was not related to the dissociation of any cofactor or modulatory subunit bound to the RyR2 channel.…”

Section: Resultsmentioning

confidence: 99%

“…Protamine is clinically utilized to reverse heparin overdose and has been shown to display significant cardiotoxic effects, including decreased cardiac output and electrocardiographic disturbances [31]. Studies performed using isolated myocytes revealed multiple effects of protamine, including changes in cardiomyocyte contraction (depressed contraction at 3 Hz but enhanced at 0.5 Hz or at lower rates), partial membrane depolarization, rise in resting tension and appearance of rested state rapid cooling contractures [61].…”

Section: Discussionmentioning

confidence: 99%

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Voltage-Dependent Modulation of Cardiac Ryanodine Receptors (RyR2) by Protamine

Diaz-Sylvester

Copello

2009

PLoS ONE

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It has been reported that protamine (>10 µg/ml) blocks single skeletal RyR1 channels and inhibits RyR1-mediated Ca2+ release from sarcoplasmic reticulum microsomes. We extended these studies to cardiac RyR2 reconstituted into planar lipid bilayers. We found that protamine (0.02–20 µg/ml) added to the cytosolic surface of fully activated RyR2 affected channel activity in a voltage-dependent manner. At membrane voltage (Vm; SR lumen - cytosol) = 0 mV, protamine induced conductance transitions to several intermediate states (substates) as well as full block of RyR2. At Vm>10 mV, the substate with the highest level of conductance was predominant. Increasing Vm from 0 to +80 mV, decreased the number of transitions and residence of the channel in this substate. The drop in current amplitude (full opening to substate) had the same magnitude at 0 and +80 mV despite the ∼3-fold increase in amplitude of the full opening. This is more similar to rectification of channel conductance induced by other polycations than to the action of selective conductance modifiers (ryanoids, imperatoxin). A distinctive effect of protamine (which might be shared with polylysines and histones but not with non-peptidic polycations) is the activation of RyR2 in the presence of nanomolar cytosolic Ca2+ and millimolar Mg2+ levels. Our results suggest that RyRs would be subject to dual modulation (activation and block) by polycationic domains of neighboring proteins via electrostatic interactions. Understanding these interactions could be important as such anomalies may be associated with the increased RyR2-mediated Ca2+ leak observed in cardiac diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Voltage-Dependent Modulation of Cardiac Ryanodine Receptors (RyR2) by Protamine

Diaz-Sylvester

Copello

2009

PLoS ONE

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“…Protamine, which is a polycationic peptide existing in the mature testis of fish with a molecular weight of 4.0-4.5 KDa [6,7], is known to possess a variety of biological activities such as bacterial inhibition, anticoagulation, and promoting digestion [8][9][10]. In a previous report, histone has been determined as a nucleoprotein that tightly bounds to the DNA [11].…”

Section: Introductionmentioning

confidence: 99%

Extraction, Identification, Modification, and Antibacterial Activity of Histone from Immature Testis of Atlantic salmon

et al. 2020

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In the present study, histone from immature testis of Atlantic salmon was extracted and identified, and its antibacterial activity after enzymolysis was investigated. Histone extracted from Atlantic salmon (Salmo salar) testis using the acid extraction method was successfully identified by LC-MS/MS, and revealed significant inhibitory activity on both the Gram-negative and Gram-positive bacteria. With a low concentration of 10 mg/mL, the observed inhibitory zone diameter (IZD) could significantly reach up to 15.23 mm. After modification of enzymatic hydrolysis by pepsin, histone could be digested to three fragments, while the antibacterial activity increased up to 57.7%. All the results suggested the leftovers from commercial fishing could be utilized for the extraction of antimicrobial peptides.

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“…Some studies have suggested that the cardiovascular depressant actions of protamine sulphate result from a direct effect producing aberrant conduction within the heart that may result in deleterious effects on heart function typical of myocardial disease. 1 The main mechanism of action of protamine sulphate in smooth muscle is via interactions with calcium influxes and/or calcium ion release from intracellular stores. 2 The main role of calcium ions in contraction of uterine smooth muscle is the activation of calcium ion calmodulin-dependent protein kinase and phosphorylation of myosin, a process dependent on ATP consumption.…”

Section: Introductionmentioning

confidence: 99%

Diethyldithiocarbamate potentiates the effects of protamine sulphate in the isolated rat uterus

Oreščanin-Dušić¹,

Milovanović

Blagojević³

et al. 2009

Redox Report

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Protamine sulphate causes potassium ion channel-mediated relaxation of spontaneous and calcium ion-induced contractions of the isolated rat uterus. Diethyldithiocarbamate (DDC) potentiated the effect of protamine sulphate. A mechanism for DDC's action was postulated on the basis of its interactions with divalent iron ions and Cu,Zn-SOD. DDC chelates divalent iron ions creating DDC-iron (Fe-DDC) complexes. Fe-DDC forms stable NO-Fe-DDC(2) complexes by NO scavenging and de-nitrosylation processes, which in combination with DDC (5 mM) provoke inhibition of Cu,Zn-SOD resulting in specific oxidative conditions culminating in potassium ion channel opening, membrane hyperpolarisation, inhibition of calcium ion influx and subsequent muscle relaxation. As Fe-DDC and NO-Fe-DDC(2) complexes exclude divalent iron ions from participating in the hydroxyl radical generating Fenton reaction, DDC can also prevent iron-related pathophysiological manifestations. Such permissive roles of DDC open the possibility for application of its pharmacological form (disulfiram) to a wider spectrum of pathophysiological conditions related to smooth muscles.

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Protamine is a low molecular weight polycationic amine that produces actions on cardiac muscle

Cited by 22 publications

References 28 publications

Voltage-Dependent Modulation of Cardiac Ryanodine Receptors (RyR2) by Protamine

Voltage-Dependent Modulation of Cardiac Ryanodine Receptors (RyR2) by Protamine

Extraction, Identification, Modification, and Antibacterial Activity of Histone from Immature Testis of Atlantic salmon

Diethyldithiocarbamate potentiates the effects of protamine sulphate in the isolated rat uterus

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