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O. PALYHIN (2020) 'CARDIAC CHANNELS IN CAVEOLIN-RICH MEMBRANE DOMAINS: REGULATION OF SINGLE SODIUM CURRENT AMPLITUDE' in O.A. Krishtal, E.A. Lukyanetz (Eds.), ESSAYS ON NEUROPHYSIOLOGY BY PLATON KOSTYUK AND HIS STUDENTS, AKADEMPERIODYKA, pp. 293-298

CARDIAC CHANNELS IN CAVEOLIN-RICH MEMBRANE DOMAINS: REGULATION OF SINGLE SODIUM CURRENT AMPLITUDE

O. PALYHIN

    Department of Biological Sciences, University of Warwick, Great Britain
DOI: https://doi.org/10.15407/biph.books.EssNeur.293


Abstract

Neurohumoral regulation of the cardiac sodium channel (Nav1.5) via the stimulation of β-adrenergic receptors is of particular interest in light of its effect under conditions of stress and cardiac disease. Beta-adrenoceptor stimulation affects the Nav1.5 channel by at least two major parallel pathways. The classical signal transduction paradigm is dependent on the phosphorylation of ion channels by protein kinase A (PKA-dependent pathway). Phosphorylation of the Nav1.5 channel results in changes in the voltagependent availability, kinetics of current decay and the amplitude of the whole-cell current. Gsα also diverges to interact with downstream proteins (PKA-independent). The overall objective of our research is to understand the PKA-independent signaling pathway of the β-adrenergic enhancement of Nav1.5 channels in adult ventricular cardiomyocytes. The sodium channel increase is central to the increase in action potential upstroke velocity and thus the increase in conduction velocity in the heart. Recently, we made observation that sodium cardiac channels function can be modulated by caveolin-3 in ventricular cells.

Keywords: Cardiac sodium channel, Nav1.5, beta-adrenergic receptors, caveolae, caveolin-3, Gsα signaling, PKA-independent pathway, sodium current , ion channel regulation, ventricular cardiomyocytes, long QT syndrome, sudden infant death syndrome, membrane domains, signal transduction, caveolar ion channels, isoproterenol, QX-314, tetrodotoxin, single-channel recordings, electrophysiology, cardiac excitability, arrhythmia, cardiac hypertrophy.

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References

  1. Alpert LA, Fozzard HA, Hanck DA, Makielski JC. 1989a. Is there a second external lidocaine binding site on mammalian cardiac cells? Am J Physiol 257: H79-H84. CrossRef PubMed
  2. Alpert LA, Fozzard HA, Hanck DA, Makielski JC. 1989b. Is there a second external lidocaine binding site on mammalian cardiac cells? Am J Physiol 257: H79-H84. CrossRef PubMed
  3. Cagliani R, Bresolin N, Prelle A, Gallanti A, Fortunato F, Sironi M, Ciscato P, Fagiolari G, Bonato S, Galbiati S, Corti S, Lamperti C, Moggio M, Comi GP. 2003. A CAV3 microdeletion differentially affects skeletal muscle and myocardium. Neurology 61: 1513-1519. CrossRef PubMed
  4. Hnasko R, Lisanti MP. 2003. The biology of caveolae: lessons from caveolin knockout mice and implications for human disease. Mol Interv 3: 445-464. CrossRef PubMed
  5. Lu T, Lee HC, Kabat JA, Shibata EF. 1999. Modulation of rat cardiac sodium channel by the stimulatory G protein alpha subunit. J Physiol 518 (Pt 2): 371-384. CrossRef PubMed PubMedCentral
  6. Maguy A, Hebert TE, Nattel S. 2006. Involvement of lipid rafts and caveolae in cardiac ion channel function. Cardiovasc Res 69: 798-807. CrossRef PubMed
  7. Matsuda JJ, Lee H, Shibata EF. 1992. Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation. Circ Res 70: 199-207. CrossRef PubMed
  8. Ono K, Fozzard HA, Hanck DA. 1993. Mechanism of cAMP-dependent modulation of cardiac sodium channel current kinetics. Circ Res 72: 807-815. CrossRef PubMed
  9. Palygin OA, Pettus JM, Shibata EF. 2008. Regulation of caveolar cardiac sodium current by a single Gsalpha histidine residue. Am J Physiol Heart Circ Physiol 294: H1693-H1699. CrossRef PubMed
  10. Park DS, Woodman SE, Schubert W, Cohen AW, Frank PG, Chandra M, Shirani J, Razani B, Tang B, Jelicks LA, Factor SM, Weiss LM, Tanowitz HB, Lisanti MP. 2002. Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype. Am J Pathol 160: 2207-2217. CrossRef PubMed
  11. Qu Y, Rogers J, Tanada T, Scheuer T, Catterall WA. 1995. Molecular determinants of drug access to the receptor site for antiarrhythmic drugs in the cardiac Na+ channel. Proc Natl Acad Sci U S A 92: 11839-11843. CrossRef PubMed PubMedCentral
  12. Schreibmayer W. 1999. Isoform diversity and modulation of sodium channels by protein kinases. Cell Physiol Biochem 9: 187-200. CrossRef PubMed
  13. Vatta M, Ackerman MJ, Ye B, Makielski JC, Ughanze EE, Taylor EW, Tester DJ, Balijepalli RC, Foell JD, Li Z, Kamp TJ, Towbin JA. 2006. Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 114: 2104-2112. CrossRef PubMed
  14. Yarbrough TL, Lu T, Lee HC, Shibata EF. 2002. Localization of cardiac sodium channels in caveolin-rich membrane domains: regulation of sodium current amplitude. Circ Res 90: 443-449. CrossRef PubMed
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