1 / 27

Electrical System of the Heart

Molecular Determinants of Na + and K + Channel Regulation in Heart: Ion Channels as Targets of Neurohormones and Drugs. Electrical System of the Heart. Ion Channels in Heart.  -Adrenergic Stimulation Shortens AP Duration. 10 -9. 10 -8. 10 -7. 10 -6. 10 -5. [Noradrenaline] (M).

peyton
Download Presentation

Electrical System of the Heart

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Molecular Determinants of Na+ and K+ Channel Regulation in Heart:Ion Channels as Targets of Neurohormones and Drugs

  2. Electrical System of the Heart

  3. Ion Channels in Heart

  4. -AdrenergicStimulation Shortens AP Duration

  5. 10-9 10-8 10-7 10-6 10-5 [Noradrenaline] (M) Normalized change in ICa Normalized change in IKs (Kass & Wiegers, J Physiol. 1982)

  6. Targeting Proteins

  7. AKAPS

  8. KCNQ1 KCNE1 A (Splawski et al, Circ102;1178-85, 2000) B KCNQ1 KCNQ1+KCNE1 50 pA/pF 200 pA/pF 0.5 s

  9. The KCNQ1 Macromolecular Complex

  10. LZ mutation ablates functional up regulation wtKCNQ1+KCNE1(E1)+yotiao(Y) LZm KCNQ1+E1+Y

  11. State-Dependent Block Na Channels as models of drug targets

  12. Voltage-Gated Sodium Channels

  13. Na Channel Stucture

  14. Gating and S4 Segments

  15. Molecular Determinants of Inactivation

  16. Inherited Mutations and Cardiac Arrhythmias

  17. Lessons from Rare Genetic Disorders

  18. Mutations of inactivation gate alter inactivation I II III IV + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + E1784K D1790G IFM KPQ NH2 Dins1795 COOH A1924T

  19. Clinical studies: linking sympathetic nerve stimulation to Long-Sydrome (LQT-1) Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Schwartz PJ, et al. Circulation 2001 Jan 2;103(1):89-95. "LQT1 patients experienced the majority of their events (62%) during exercise, and only 3% occurred during rest/sleep. "

  20. J Am Coll Cardiol 2001 Feb;37(2):562-8 A founder mutation of the potassium channel KCNQ1 in long QT syndrome: implications for estimation of disease prevalence and molecular diagnostics. Piippo K, Swan H, Pasternack M, Chapman H, Paavonen K, Viitasalo M, Toivonen L, Kontula K. Department of Medicine, University of Helsinki, Finland.

  21. G589D KCNQ1+E1+Y Mutation G589D ablates channel regulation

  22. Drugs Can Induce LQT

More Related