ca 2+ release mechanisms in cardiac & skeletal muscle objectives methodology:methodology:...
TRANSCRIPT
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Ca2+ release mechanisms in cardiac & skeletal muscle
OBJECTIVES• Methodology:
• Chimeric proteins• FRET
• Differences in Ca2+ release between cardiac and skeletal muscle
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INTRODUCTION
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Ca2+ channel characteristics
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Voltage sensitive Ca2+ channel molecular structure
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Mammalian Ca2+ channel genes
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SR Ca2+ release channel – Ryanodine receptor (RyR)
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RyR molecular structure
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Mammalian ligand-gated Ca2+ channel genes
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DHPR-RyR molecular arrangment
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Ca2+ release in skeletal muscle
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Ca2+ release in cardiac muscle
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DISCUSSION
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1.5 nA
15 nA
10 nA
Cardiac sequenceSkeletal muscle sequence
pCac6 (Sk)
pCARD1
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pCac6 (Sk)
pCARD1
Ca2+ + 0 / Cd2+
CELL SHORTENING
Cardiac sequenceSkeletal muscle sequence
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I II III IV
II-III LOOP
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Serine687 to alanine (S687A)Serine – PKA (only in Sk)
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I II III IV
II-III LOOP
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Dyspedic myotubes
Region with RyR-2 cDNA
injection
Normal myotubes
Dyspedic myotubes with RyR-2
Ca2+ transient during spontaneous contractions
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Normal myotubes Dyspedic myotubes with RyR-2
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Ca2+ currentRyR-2
expressing Dyspedic myotubes
Ca2+ current & [Ca2+]i
RyR-2 expressing Dyspedic myotubes
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Ca2+ currentCSk3
expressing Dyspedic myotubes
Ca2+ transientDyspedic myotubes
Electrically evoked
Spontaneous
Failure (electrical)
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