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

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Presentation transcript:

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

INTRODUCTION

Ca 2+ channel characteristics

Voltage sensitive Ca 2+ channel molecular structure

Mammalian Ca 2+ channel genes

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

RyR molecular structure

Mammalian ligand-gated Ca 2+ channel genes

DHPR-RyR molecular arrangment

Ca 2+ release in skeletal muscle

Ca 2+ release in cardiac muscle

DISCUSSION

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

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

I II III IV II-III LOOP

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

I II III IV II-III LOOP

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

Normal myotubesDyspedic myotubes with RyR-2

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

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