1. Ca 2+ release mechanisms in cardiac & skeletal muscle OBJECTIVES Methodology:Methodology: Chimeric proteinsChimeric proteins FRETFRET Differences in Ca 2+ release between cardiac and skeletal muscleDifferences in Ca 2+ release between cardiac and skeletal muscle

2. INTRODUCTION

3. Ca 2+ channel characteristics

4. Voltage sensitive Ca 2+ channel molecular structure

5. Mammalian Ca 2+ channel genes

6. SR Ca 2+ release channel – Ryanodine receptor (RyR)

7. RyR molecular structure

8. Mammalian ligand-gated Ca 2+ channel genes

9. DHPR-RyR molecular arrangment

10. Ca 2+ release in skeletal muscle

11. Ca 2+ release in cardiac muscle

13. DISCUSSION

14. 1.5 nA 15 nA 10 nA Cardiac sequence Skeletal muscle sequence pCac6 (Sk) pCARD1

15. pCac6 (Sk) pCARD1 Ca 2+ + 0 / Cd 2+ CELL SHORTENING Cardiac sequence Skeletal muscle sequence

16. I II III IV II-III LOOP

17. Serine 687 to alanine (S687A) Serine – PKA (only in Sk)

18. I II III IV II-III LOOP

20. Dyspedic myotubes Region with RyR-2 cDNA injection Normal myotubes Dyspedic myotubes with RyR-2 Ca 2+ transient during spontaneous contractions

21. Normal myotubesDyspedic myotubes with RyR-2

22. Ca 2+ current RyR-2 expressing Dyspedic myotubes Ca 2+ current & [Ca 2+ ] i RyR-2 expressing Dyspedic myotubes

23. Ca 2+ current CSk3 expressing Dyspedic myotubes Ca 2+ transient Dyspedic myotubes Electrically evoked Spontaneous Failure (electrical)