Voltage-dependent modulation of cardiac ryanodine receptors (RyR2) by protamine.

It has been reported that protamine (>10 microg/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 microg/ml)...

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Autores principales:	Paula L Diaz-Sylvester, Julio A Copello
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29734ad6b6524de9986ce53286e30318
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spelling	oai:doaj.org-article:29734ad6b6524de9986ce53286e303182021-11-25T06:27:23ZVoltage-dependent modulation of cardiac ryanodine receptors (RyR2) by protamine.1932-620310.1371/journal.pone.0008315https://doaj.org/article/29734ad6b6524de9986ce53286e303182009-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20016815/?tool=EBIhttps://doaj.org/toc/1932-6203It has been reported that protamine (>10 microg/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 microg/ml) added to the cytosolic surface of fully activated RyR2 affected channel activity in a voltage-dependent manner. At membrane voltage (V(m); SR lumen-cytosol) = 0 mV, protamine induced conductance transitions to several intermediate states (substates) as well as full block of RyR2. At V(m)>10 mV, the substate with the highest level of conductance was predominant. Increasing V(m) 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 approximately 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.Paula L Diaz-SylvesterJulio A CopelloPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 12, p e8315 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paula L Diaz-Sylvester Julio A Copello Voltage-dependent modulation of cardiac ryanodine receptors (RyR2) by protamine.
description	It has been reported that protamine (>10 microg/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 microg/ml) added to the cytosolic surface of fully activated RyR2 affected channel activity in a voltage-dependent manner. At membrane voltage (V(m); SR lumen-cytosol) = 0 mV, protamine induced conductance transitions to several intermediate states (substates) as well as full block of RyR2. At V(m)>10 mV, the substate with the highest level of conductance was predominant. Increasing V(m) 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 approximately 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.
format	article
author	Paula L Diaz-Sylvester Julio A Copello
author_facet	Paula L Diaz-Sylvester Julio A Copello
author_sort	Paula L Diaz-Sylvester
title	Voltage-dependent modulation of cardiac ryanodine receptors (RyR2) by protamine.
title_short	Voltage-dependent modulation of cardiac ryanodine receptors (RyR2) by protamine.
title_full	Voltage-dependent modulation of cardiac ryanodine receptors (RyR2) by protamine.
title_fullStr	Voltage-dependent modulation of cardiac ryanodine receptors (RyR2) by protamine.
title_full_unstemmed	Voltage-dependent modulation of cardiac ryanodine receptors (RyR2) by protamine.
title_sort	voltage-dependent modulation of cardiac ryanodine receptors (ryr2) by protamine.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/29734ad6b6524de9986ce53286e30318
work_keys_str_mv	AT paulaldiazsylvester voltagedependentmodulationofcardiacryanodinereceptorsryr2byprotamine AT julioacopello voltagedependentmodulationofcardiacryanodinereceptorsryr2byprotamine
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Voltage-dependent modulation of cardiac ryanodine receptors (RyR2) by protamine.

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