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. -Adrenergic Stimulation Shortens AP Duration

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

6. Targeting Proteins

7. AKAPS

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

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

20. Inherited Mutations and Cardiac Arrhythmias

21. Lessons from Rare Genetic Disorders

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

24. 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. "

25. 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.

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

27. Drugs Can Induce LQT