The grant details show the name of the PI, active dates of the project, the funding institute and the abstract of the grant. This abstract is what is used to create the Fingerprint of the grant. The source of grants for this application is NIH ExPORTER, so only NIH grants are included. More information is available at http://projectreporter.nih.gov/ExPORTER/default.aspx.
MECHANISMS OF MODIFIED NA CHANNELS IN CARDIAC ISCHEMIA
17 June 1994 - 31 May 1999
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Total Funding: $ 502,984
This new application for three years of support has the long term objective to investigate mechanisms for modified ion channel function in cardiac ischemia. The ischemic metabolite lysophosphatidylcholine (LPC) has long been implicated as a key mediator of electrophysiological changes and arrhythmias in acute ischemia. Indirect evidence has suggested that both LPC and ischemia disturb the cytoskeleton. The cytoskeleton disrupting agent cytochalasin modified Na channel gating similarly to that of how LPC. This suggests that the mechanism for the LPC effect on Na channels may be through the cytoskeleton. Alternatively, LPC may act through a mechanism not involving the cytoskeleton such as lipid channel protein interactions or direct effects. LPC has been little studied at the cellular level, and the role of the cytoskeleton in cardiac ion channels gating is unknown. Both are likely to be important links in the pathogenesis of ischemia. In this proposal, the kinetics of LPC-modified cardiac Na channels will be fully described by patch clamping isolated rat and rabbit cardiac cells (Aim 1). The role of the cytoskeleton in Na channel gating will be investigated by using cytoskeleton disrupting (e.g., colchicine, cytochaIasin) and stabilizing (e.g., phalloidin and taxol) agents, cytoskeleton elements (actin, spectrin and linkage protein ankyrin) and antibodies to these elements (Aim 2). The interaction of antiarrhythmic drugs (lidocaine, flecainide, quinidine) with these modified channels will be studied by patch clamp (Aim 3). Mathematical models will be used for both channel gating and drug-channel interaction. These results may help explain why ischemic tissue is apparently more sensitive to the action of some antiarrhythmic drugs as well as cytoskeleton role in Na channel function. Since cardiac arrhythmias ischemic heart disease remain major public health problems, knowledge of the underlying mechanisms may lead to better understanding of cardiac arrhythmias and provide insight into treatment.
21 Resulting Publications
Sudhish Mishra; Nidas A Undrovinas; Victor A Maltsev; Vitaliy Reznikov; Hani N Sabbah; Albertas UndrovinasAmerican journal of physiology. Heart and circulatory physiology 2011;301(4):H1596-605.
Albertas Undrovinas; Victor A MaltsevCardiovascular & hematological agents in medicinal chemistry 2008;6(4):348-59.
Victor A Maltsev; John W Kyle; Sudhish Mishra; Abertas UndrovinasAmerican journal of physiology. Heart and circulatory physiology 2008;295(2):H667-76.
Victor A Maltsev; Vitaliy Reznikov; Nidas A Undrovinas; Hani N Sabbah; Albertas UndrovinasAmerican journal of physiology. Heart and circulatory physiology 2008;294(4):H1597-608.
Victor A Maltsev; Albertas UndrovinasProgress in biophysics and molecular biology 2008;96(1-3):421-51.
Victor A Maltsev; Norman Silverman; Hani N Sabbah; Albertas I UndrovinasEuropean journal of heart failure 2007;9(3):219-27.
Albertas I Undrovinas; Luiz Belardinelli; Nidas A Undrovinas; Hani N SabbahJournal of cardiovascular electrophysiology 2006;17 Suppl 1():S169-S177.
Victor A Maltsev; Albertas I UndrovinasCardiovascular research 2006;69(1):116-27.
Stephen Zicha; Victor A Maltsev; Stanley Nattel; Hani N Sabbah; Albertas I UndrovinasJournal of molecular and cellular cardiology 2004;37(1):91-100.
Albertas I Undrovinas; Victor A Maltsev; John W Kyle; Norman Silverman; Hani N SabbahJournal of molecular and cellular cardiology 2002;34(11):1477-89.
V A Maltsev; H N Sabbab; A I UndrovinasCellular and molecular life sciences : CMLS 2002;59(9):1561-8.
V A Maltsev; H N Sabbah; A I UndrovinasJournal of molecular and cellular cardiology 2001;33(5):923-32.
A I Undrovinas; V A Maltsev; H N SabbahCellular and molecular life sciences : CMLS 1999;55(3):494-505.
V A Maltsev; H N Sabbah; R S Higgins; N Silverman; M Lesch; A I UndrovinasCirculation 1998;98(23):2545-52.
A I Undrovinas; V A MaltsevJournal of molecular and cellular cardiology 1998;30(8):1665-70.
V A Maltsev; H N Sabbah; M Tanimura; M Lesch; S Goldstein; A I UndrovinasCellular and molecular life sciences : CMLS 1998;54(6):597-605.
V A Maltsev; A I UndrovinasCellular and molecular life sciences : CMLS 1998;54(2):148-51.
V A Maltsev; A I UndrovinasThe American journal of physiology 1997;273(4 Pt 2):H1832-40.
A I Undrovinas; J C MakielskiThe American journal of physiology 1996;271(2 Pt 2):H790-7.
G S Shander; A I Undrovinas; J C MakielskiJournal of molecular and cellular cardiology 1996;28(4):743-53.
A I Undrovinas; G S Shander; J C MakielskiThe American journal of physiology 1995;269(1 Pt 2):H203-14.
This section shows information that has been computed by using the fingerprint of the grant, including related publications, related experts and related grants - all with fingerprints representing significant amounts of overlap between their fingerprint and this grant. The red dots indicate whether those experts or terms actually appear within this grant, showing potential and actual connections.
Undrovinas, Albertas I
15 July 2003 - 30 June 2007
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Total Funding: $ 847,637
ATCHISON, WILLIAM D
1 July 1985 - 31 March 2001
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Total Funding: $ 2,019,253
BHALLA, DEEPAK K
1 March 1985 - 29 February 1988
NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
Total Funding: $ 492,777
Sony Jacob; Omaima A Ali; Victoria Pidlaoan; Apurva O Badheka; Nicholas Z KerinAmerican journal of therapeutics 2011;18(3):241-60.
J Kupersmith; M Holmes-Rovner; A Hogan; D Rovner; J GardinerProgress in cardiovascular diseases 1995;37(5):307-46.
A I Undrovinas; N A Burnashev; I A Fledervish; K Dzheniuari; I Iuriavichius; Zh Ridl; D Zablotskaĭte; Ch Siuĭ; L V RozenshtraukhKardiologiia 1990;30(9):69-73.
Appears in this Publication
Author of this Publication